Man make decisions: good decisions for progress, or less good decisions consequent in stagnation and squanders. At a spare of moment, anyone could make a bad decision in fragility, attributed by psychological and physical exhaustion.
Important decisions on issues affecting masses are therefore wisely made democratically. Like any statistical method, more opinions counted there are, less deviated decisions are to be made, provided that a substantial numbers of experienced experts are analysing and assessing likely outcomes in a long-term; a foresighted decision, fair and appropriate to the circumstances, could then be reached. Such a collective intelligence works for the whole group to benefit.
Such successes at a large scale emerges as a combined efforts of smaller groups, each consisting of individuals capable of synthesising highly imaginative complex ideas. Mutual aspirations glue groups sharing aspirations, resulting in synergistic productivity in rapid succession.
In contrast, old ideas are habitually reinforced in groups of less imaginative narrow minded individuals whose emotional intelligence frequently surpasses systematic reasoning and analytical insights; the in-group individuals tend to favour the members to be at an even level, plausibly to avoid feeling inadequate in any sense. An ultimate goal of such accustomed herds are to maintain a near equilibrium among the players at comfort, with few endeavour to step forward adventurously.
Following is a summary description of relevant observations documented regarding group formation, cooperative actions among individuals and collective effects, from biologists’, psychologists’, sociologists’ and economist’ perspectives.
Herd Behaviour in Evolutionary Sense
Evidently observed in the animal kingdom, from herrings, gulls, sheep to humans, a common strategic solution for vulnerable individuals is to form flock or herd, so to increase their likelihood of survival and reproduction. An evolutionary model for group formation has demonstrated that herd formation is likely driven by predator avoidance by a confusion effect to destruct a predator through complex manoeuvres, or by a selfish herd effect driven by vulnerable individuals attempting to hide within the crowd (Wood & Ackland 2007). The latter effect was initially proposed by Hamilton (1971). Several mechanisms of predator avoidance have been described, additionally including collective vigilance and dilution of risks (reviewed by Krause & Ruxon 2002).
Herding with Mirroring
Herding in primates heavily values interrelation between individuals. Monitoring the others and imitating is a standard procedure in communicating and learning among groups of monkeys and humans (Horner et al. 2006; Palagi et al. 2009; Prinz 2005; Shepherd et al. 2009). Such mirroring actions involve activation of so-called “mirror neurones” in motor-visual and auditory-visual systems between the two communicators (reviewed by Fabbri-Destro & Rizzolatti 2008; Hari & Kujala 2009). Mirror neurones are not unique properties of primates, as these have also been found in the forebrain of songbirds (Prather et al. 2008). In primates, non-verbal vocalisation endorsed with positive emotions cause mirror neurones firing, facilitating social bonding thereby (Warren et al. 2006). Mirror neurones in Brodmann area 44 of inferior frontal gyrus cortices have been shown to be critically involved in emotional empathy (Shamay-Tsoory, Aharon-Peretz & Perry 2009). By the mirroring effect humans learn signals between individuals and increase awareness to certain stimuli from observing how others respond to it; such observation based social cognition skill is applied extensively in human communication (reviewed by Frith 2008).
Cooperative Behaviours in Social Networks
Several studies on social networks have investigated structures in human interactions and evolution of cooperative behaviours. Although in large unstructured populations individuals are less likely to cooperate (Enquist & Limar 1993), frequent interactions in a fixed social network allow cooperation to evolve without motivating factors such as reputation effect and strategic complexity (Nowak 2006; Ohtsuki et al. 2006).
Certain human conditions influenced by affective status are known to be socially contagious. The conditions including obesity, positive mood status, ideations, attitudes, altruism etc can spread among people at least with three degrees of separation through direct or indirect interactions; such phenomena are observable excluding the possibility of the effects arising solely due to selection bias in a “birds of feathers flock together” fashion (Fowler & Christakis 2009; Hill et al. 2010).
Social Influence Online
Since humans have developed a mean of remotely communicating through digital media, most notably via the world-wide-web thanks to Berners-Lee’s project in CERN in 1989-1990, the internet has offered a way to express opinions, all in equal opportunities with freedom of speech in this global public domain, where to learn and share knowledge; with the information readily be available with frequent updates, online cultures have flourished and still evolving.
Through social network sites such as Facebook, users can view and share connections with selected others in the system. In the online environment, a form of social influence emerges as individuals’ interpersonal communications merges with global mass media, consequentially influencing consumption behaviour of cultural products (e.g. books, music, DVDs etc) or choices of lifestyles (Onnela & Reed-Tsochas 2009).
Social Influences On Human Acts
Socio-psychologists have observed that decisions made by individuals are influenced by others’ decisions already made, or anticipated to be made (Cialdini 2001).
Human action could be affected by awareness of being subjected, as seen in Hawthorne effect which describes an observed increase in short-term productivity by workers was due to elevated motivation by the experimental settings, wherein the workers were allowed to work in a small group of selected co-workers, receiving attentions and communications by cooperative supervisors; hence the increased productivity observed was not by each specified condition purposefully measured in the study; evidently, the productivity of the workers declined after the study ended. Participating in a study for something novel might have also contributed to elevate their motivation to work, for an additional sense of purpose in contrast to the usual dullness of the work.
A disturbing finding on how social setting could affect human behaviour was that authority figures can enforce acts on individuals against their innate wishes and moral standards through their obedience (Milgram 1969). In line with the Milgram’s study, Stanford prison experiment have demonstrated that placing individuals in a specific situation with a given role influences how they act and behave, even to an atrocity (Zimbardo 1971).
On the other hand, interdependent decision making between individuals in crowd could influence collective behaviours of an orderly crowd in such a way to ignite a riot (Granovetter 1978).
In contrast, expectations on others’ behaviours and individuals’ shyness in crowd can produce bystander effect: people are less likely to offer help to the one who needs it when there are others around (Milgram 1970).
Behavioural Effects On Economy
Herd behaviour has notably been observed among economists: stock market bubbles are formed by excess buying driven by a chain of greed, of those making profits and copying behaviour by others jumping on the bandwagon; then market clashes by panic selling in fears of bubble bursting, accompanied with loss aversion followed by risk aversion.
Major challenge currently faced globally is a food security. Immediate concerns have been existing particularly in developing nations, due to growing populations, and climate changes causing drafts and flooding. Such concerns cause instability in food prices due to speculations made by market traders in herd, displaying hoarding behaviour. Unlike other commodity, such behaviours which cause price elevation of staple food impose much bigger effects on populations, because food insecurity is a matter of life-threat among individuals with low-income. Driven by increased anxiety, fears, and dissatisfaction, individuals aggregate purposefully for demonstrations and riots as there have been in recent years. The issue on food security has been reviewed and discussed by Timmer (2010).
Concluding Remarks
In every circumstance, humans constantly make decisions for next own actions, and actions to be taken by others with an authority to do so, for short-term and long-term benefits. Each decision made, and how every one behaves often affects the behaviours of others.
References
Cialdini RB. 2001. Influence: Science and Practice. Needham Heights, MA: Allyn and
Bacon.
Enquist M & Leimar O. 1993. The evolution of cooperation in mobile organisms. Anim
Behav 45: 747–757. doi:10.1006/anbe.1993.1089
Fabbri-Destro M & Rizzolatti G. 2008. Mirror Neurons and Mirror Systems in Monkeys and Humans. Physiology. 23: 171–179.
Fowler JH & Christakis NA. 2009. Cooperative behavior cascades in human social networks. PNAS. 107: 5334–5338.
Frith C. 2008. Social cognition. Phil. Trans. R. Soc. B. 363: 2033–2039
Granovetter, M. S. 1978. ‘Threshold Models of Collective Behavior.’ American Journal of Sociology 83: 1420–43.
Hamilton WD. 1971. Geometry for the selfish herd. J Theor Biol. 31:295–311.
Hari R & Kujala MV. 2009. Brain Basis of Human Social Interaction: From Concepts to Brain
Imaging. Physiol Rev 89: 453–479.
Hill AL et al. 2010. Infectious Disease Modeling of Social Contagion in Networks. PLoS Computational Biol. 6: e1000968.
Horner V et al. 2006. Faithful replication of foraging techniques along cultural transmission chains by chimpanzees and children. PNAS. 103: 13878–13883.
Krause J & Ruxton GD. 2002. Living in groups. Oxford: Oxford University Press.
Milgram, S. 1969. Obedience to Authority. New York: Harper and Row.
Milgram, S. 1970. The Experience of Living in Cities. Science. 167: 1461-1468.
Nowak MA. 2006. Five rules for the evolution of cooperation. Science 314: 1560–1563.
Onnela JP & Reed-Tsochas F. 2009. Spontaneous emergence of social influence in online systems. PNAS. 107: 18375–18380.
Ohtsuki H et al. 2006. A simple rule for the evolution of cooperation on graphs and social networks. Nature 441:502–505.
Palagi et al. 2009. Contagious yawning in gelada baboons as a possible expression of empathy. PNAS. 106: 19262-19267.
Prather JF et al. 2008. Precise auditory-vocal mirroring in neurons for learned vocal communication. Nature 451: 305–310.
Prinz JJ. 2005 Imitation and moral development. In Perspectives on imitation—from neuroscience to social science, vol. 2: imitation, human development, and culture (eds S. Hurley & N. Chater), pp. 267–282. Cambridge, MA: MIT Press.
Shamay-Tsoory SG, Aharon-Peretz J & Perry D. 2009. Two systems for empathy: a double dissociation between emotional and cognitive empathy in inferior frontal gyrus versus ventromedial prefrontal lesions. Brain. 132: 617–627.
Shepherd SV et al. 2009. Mirroring of attention by neurons in macaque parietal cortex. PNAS. 106: 9489–9494.
Timmer CP. 2010. Agriculture Development and Nutrition Security Special Feature: Behavioral dimensions of food security. PNAS. Early edition.
Warren JE et al. 2006. Positive Emotions Preferentially Engage an Auditory–Motor “Mirror” System. J Neurosci. 26: 13067–13075.
Wood AJ & Ackland GJ. 2007. Evolving the selfish herd: emergence of distinct aggregating strategies in an individual-based model. Proc. R. Soc. B 274: 1637–1642.
Zimbardo PG. 1971. The power and pathology of imprisonment. Congressional Record. (Serial No. 15, 1971-10-25). Hearings before Subcommittee No. 3, of the Committee on the Judiciary, House of Representatives, Ninety-Second Congress, First Session on Corrections, Part II, Prisons, Prison Reform and Prisoner's Rights: California. Washington, DC: U.S. Government Printing Office.
Thursday, 2 June 2011
Thursday, 19 May 2011
Rules for Human Communications
The personal communications often leave some uncertainty in meanings, because it often involves compositions vague in meanings with emotion or sentiment laid underneath. What has been said or written could also be interpreted quite differently, depending on how the recipient was feeling and how the circumstances of any relevant, or irrelevant, issues surrounding were for the person at the time of the communication.
And it is not easy to place yourself in someone else’s shoes either, especially when the mind of the other do not operate in a mutual manner as one’s own.
Here is a few quotes that might help resolving the issues a bit:
“THE GOLDEN RULE
Do not do unto others as you would that they should do unto you. Their tastes may not be the same.
Never resist temptation: prove all things: hold fast that which is good.
Do not love your neighbour as yourself. If you are on good terms with yourself it is an impertinence: if on bad, an injury.
The golden rule is that there are no golden rules.”
— George Bernard Shaw 1903.
Succinctly put it that way, except the last one which is a paradoxical loop.
In addition,
if you are happened to be a stubborn, awkward person who is hardly capable of bending opinions, attitudes and beliefs in order to suite yourself to those around you, such misfits may not give up hopes because:
“The reasonable man adapts himself to the world; the unreasonable one persists in trying to adapt the world to himself. Therefore all progress depends on the unreasonable man.”
— GB Shaw 1903.
though only when the others are persuaded to follow the pursuits, either now or later on.
And it is not easy to place yourself in someone else’s shoes either, especially when the mind of the other do not operate in a mutual manner as one’s own.
Here is a few quotes that might help resolving the issues a bit:
“THE GOLDEN RULE
Do not do unto others as you would that they should do unto you. Their tastes may not be the same.
Never resist temptation: prove all things: hold fast that which is good.
Do not love your neighbour as yourself. If you are on good terms with yourself it is an impertinence: if on bad, an injury.
The golden rule is that there are no golden rules.”
— George Bernard Shaw 1903.
Succinctly put it that way, except the last one which is a paradoxical loop.
In addition,
if you are happened to be a stubborn, awkward person who is hardly capable of bending opinions, attitudes and beliefs in order to suite yourself to those around you, such misfits may not give up hopes because:
“The reasonable man adapts himself to the world; the unreasonable one persists in trying to adapt the world to himself. Therefore all progress depends on the unreasonable man.”
— GB Shaw 1903.
though only when the others are persuaded to follow the pursuits, either now or later on.
Friday, 6 May 2011
A Thought Game: Mutual Rationality Of Norms By Commonsense As Cultural Derivatives (and Let’s Get Out Of The Box for a while and see)
Here is a question: can you see whether syllogisms below make a logical sense or not (i.e. whether deductively valid or invalid)?
1. all buildings speak loudly; a hospital does not speak loudly; therefore a hospital is not a building.
2. if the sun rises then the sun is in the east; the sun is in the east; therefore the sun rises.
The syllogisms were taken from a research paper entitled “Are people with schizophrenia more logical than healthy volunteers?” published in 2007.
Owen GS, Cutting J and David AS (2007). The British Journal of Psychiatry 191: 453-454 http://bjp.rcpsych.org/cgi/doi/10.1192/bjp.bp.107.037309
The first syllogism is valid and the second is invalid. The study above found that schizophrenic patients (under anti-psychotic medications) were able to identify correctly valid non-commonsense syllogisms (e.g. 1) and invalid commonsense syllogisms (e.g. 2), being slightly but significantly better at this task than healthy participants. In discussion, the paper stated:
“ They suggest that in situations where commonsense knowledge is at stake, formal norms of rationality are violated by people with schizophrenia to a lesser extent than by healthy individuals. People with schizophrenia seem to have a bias towards theoretical rationality over and above practical rationality.”
From the finding of the study it can also be inferred that in healthy individuals a deductive reasoning unlikely is segregated effortlessly from practical commonsense knowledge when practically meaningful content is added to the context.
This further implies to a degree that deductive reasoning in an ordinary communicative language is influenced by standards (i.e. norms) taken from commonsense of mutual beliefs. Along with a question whether such standards can be absolutely identical among all individuals, this interestingly highlights the uncertain nature of the languages used in human communications. The uncertainty, however, does not necessarily affect probabilistic reasoning with numerical content. In fact, distinct usage of right and left hemispheres of the brain during deductive and probabilistic reasoning has been confirmed by positron emission tomography (PET) (Person and Osherson, 2001: Cerebral Cortex, 11:954-965); therefore the two reasoning process can be assumed not to be same.
Hence putting aside the probabilistic reasoning, the idea that language-based deductive reasoning somewhat relies on commonsense leaves us with a question on how reliable factual accuracy of conceptual worlds held by individuals or by groups relative to the absolute world as it is, unless the commonsense strictly reflect whole truths.
As often as not, a thought processing might be influenced by and relies upon an accepted standard of normality existing in each society. Ever since being born, a human steadily accumulates and updates information through observations and experiences of own as well as by the others communicating with. By doing so, a world remains being constructed in each person, in a manner the world is compatible with those of the others around (and of beyond with extended communications). The world is ordinarily malleable for cultural progresses, fluctuating tendencies of human behaviours, and dynamic nature of the physical world wherein the one resides.
Sometimes, a collective of human thoughts can emerge as an obscure assumption made by coincidences correlated with invalid logic, mostly based on and enhanced by speculative imaginations: rumours, myths and superstitions are obvious examples of such suppositions, which often stem from various emotions including fear, anxiety, hope and desire.
As we tend to take in words and exchange ideas that appeal to oneself as acceptable by so-called “gut feelings” instinctively, often without verifying factual accuracy, nor fully comprehending the meaning of it, various presumptions seep through everyday life.
Language itself is an immediate derivative of human culture and communications; unlike numbers and symbols governed by strict rules, its style, composition, and even meanings held by each word can be malleable to some extent. The uncertain nature of language was previously enquired by Ludvig Wittgenstein, and readers are referred to his study entitled Philosophical Investigation, originally published in 1953 (Blackwell publishing Ltd.), for more information on this matter in detail.
Since no individuals are free from cultural influences, we are all more or less susceptible to hold biased opinions, idiosyncratic beliefs and misapprehensions to various degrees. It therefore is useful now and again to remind ourselves to perform “reality check”, by going outside of a box to objectively oversee own social and cultural beliefs and commonsense from a standpoint of an outsider. For this purpose, there is an advantage of being in a multicultural society, for that would enable one to encounter different cultures in lively circumstances, thereby allowing cultural comparisons to be made whenever one wishes to engage with other cultures.
In comparison, certain delusional beliefs such as superstitions often remain preserved meaningfully in a more relatively closed, monocultural society, in which people live largely on assumption and expectation that others around them are alike to themselves for mutual commonsense and shared cultural beliefs. For that reason, less effort is likely made between them for precision and clarity in communications.
This point might need an attention if the mighty power of commonsense is to cloud simple logical deduction: what could be the worst possible consequence? A society or a group of people could end up holding a mass delusion. It certainly has happened before many times.
1. all buildings speak loudly; a hospital does not speak loudly; therefore a hospital is not a building.
2. if the sun rises then the sun is in the east; the sun is in the east; therefore the sun rises.
The syllogisms were taken from a research paper entitled “Are people with schizophrenia more logical than healthy volunteers?” published in 2007.
Owen GS, Cutting J and David AS (2007). The British Journal of Psychiatry 191: 453-454 http://bjp.rcpsych.org/cgi/doi/10.1192/bjp.bp.107.037309
The first syllogism is valid and the second is invalid. The study above found that schizophrenic patients (under anti-psychotic medications) were able to identify correctly valid non-commonsense syllogisms (e.g. 1) and invalid commonsense syllogisms (e.g. 2), being slightly but significantly better at this task than healthy participants. In discussion, the paper stated:
“ They suggest that in situations where commonsense knowledge is at stake, formal norms of rationality are violated by people with schizophrenia to a lesser extent than by healthy individuals. People with schizophrenia seem to have a bias towards theoretical rationality over and above practical rationality.”
From the finding of the study it can also be inferred that in healthy individuals a deductive reasoning unlikely is segregated effortlessly from practical commonsense knowledge when practically meaningful content is added to the context.
This further implies to a degree that deductive reasoning in an ordinary communicative language is influenced by standards (i.e. norms) taken from commonsense of mutual beliefs. Along with a question whether such standards can be absolutely identical among all individuals, this interestingly highlights the uncertain nature of the languages used in human communications. The uncertainty, however, does not necessarily affect probabilistic reasoning with numerical content. In fact, distinct usage of right and left hemispheres of the brain during deductive and probabilistic reasoning has been confirmed by positron emission tomography (PET) (Person and Osherson, 2001: Cerebral Cortex, 11:954-965); therefore the two reasoning process can be assumed not to be same.
Hence putting aside the probabilistic reasoning, the idea that language-based deductive reasoning somewhat relies on commonsense leaves us with a question on how reliable factual accuracy of conceptual worlds held by individuals or by groups relative to the absolute world as it is, unless the commonsense strictly reflect whole truths.
As often as not, a thought processing might be influenced by and relies upon an accepted standard of normality existing in each society. Ever since being born, a human steadily accumulates and updates information through observations and experiences of own as well as by the others communicating with. By doing so, a world remains being constructed in each person, in a manner the world is compatible with those of the others around (and of beyond with extended communications). The world is ordinarily malleable for cultural progresses, fluctuating tendencies of human behaviours, and dynamic nature of the physical world wherein the one resides.
Sometimes, a collective of human thoughts can emerge as an obscure assumption made by coincidences correlated with invalid logic, mostly based on and enhanced by speculative imaginations: rumours, myths and superstitions are obvious examples of such suppositions, which often stem from various emotions including fear, anxiety, hope and desire.
As we tend to take in words and exchange ideas that appeal to oneself as acceptable by so-called “gut feelings” instinctively, often without verifying factual accuracy, nor fully comprehending the meaning of it, various presumptions seep through everyday life.
Language itself is an immediate derivative of human culture and communications; unlike numbers and symbols governed by strict rules, its style, composition, and even meanings held by each word can be malleable to some extent. The uncertain nature of language was previously enquired by Ludvig Wittgenstein, and readers are referred to his study entitled Philosophical Investigation, originally published in 1953 (Blackwell publishing Ltd.), for more information on this matter in detail.
Since no individuals are free from cultural influences, we are all more or less susceptible to hold biased opinions, idiosyncratic beliefs and misapprehensions to various degrees. It therefore is useful now and again to remind ourselves to perform “reality check”, by going outside of a box to objectively oversee own social and cultural beliefs and commonsense from a standpoint of an outsider. For this purpose, there is an advantage of being in a multicultural society, for that would enable one to encounter different cultures in lively circumstances, thereby allowing cultural comparisons to be made whenever one wishes to engage with other cultures.
In comparison, certain delusional beliefs such as superstitions often remain preserved meaningfully in a more relatively closed, monocultural society, in which people live largely on assumption and expectation that others around them are alike to themselves for mutual commonsense and shared cultural beliefs. For that reason, less effort is likely made between them for precision and clarity in communications.
This point might need an attention if the mighty power of commonsense is to cloud simple logical deduction: what could be the worst possible consequence? A society or a group of people could end up holding a mass delusion. It certainly has happened before many times.
Thursday, 17 March 2011
The Roles of Astrocytes and Oligodendrocytes
This is a follow-up to my previous article wherein the neurogenesis of neurones in hippocampus was briefly described. For making a better view on this, I summarise a few characteristics of other cell types, which are derived from neural progenitor cells.
Neural progenitor cells that did not develop into neurones can become glioblasts, which are precursors of astrocytes or oligodendrocytes. These two types of cells are quite different morphologically and functionally; a common factor between the two is primarily to help neurones to function, and to facilitate neurotransmissions.
Astrocytes support neuronal survival and synaptic transmissions
Astrocytes are relatively large cells with sponge-like appearance, extending multiple dendritic protrusions which display finely intricate branching patterns. Astrocytes can be found between blood vessels and neurones, or by synapses.
Basic Role 1: Astrocytes As a Crucial Supplier to Neurones
At blood vessels, astrocytes participate in forming the blood-brain barrier, which selectively takes necessary substances from the circulation into the brain. It sieves out larger and charged molecules sufficiently, but lipophilic substances (e.g. alcohol, synthetic lipid-soluble compounds) that permeate through the cell membranes cannot be excluded by this mechanism; hence such substances elicit central effects.
The blood also carries glutamate, an excitatory neurotransmitter, to the brain. In order to avoid neurones to get excited unnecessarily, neurones do not make a direct contact with the blood vessels. Astrocytes can collect glutamate via glutamate transporters (EAAT1-3) and convert that to a less excitable glutamine.
Glucose, the energy source, is also carried in the blood. Astrocytes collect glucose from the blood using their glucose transporter (GLUT1), and give much of that to energy-intensive neurones after converting it to lactate, which is readily utilisable in ATP synthesis.
Basic Role 2: The Synapses Are Protected by Astrocytes
At synapses, glutamate needs to be removed soon after the transmission, for not only a prolonged excitation cause seizures and paralysis by hyper-activating neurones, an excessive excitation could destroy neurones. The availability of glutamate at synapses therefore needs a close monitoring: astrocytes do this by collecting excess glutamate.
Q&A: G-Protein Couple Receptors and Calcium Oscillation in Astrocytes
The roles of astrocytes mentioned above are important for neurones to function, but the story does not stop there. Astrocytes in fact express various receptors for neurotransmitters including: adenosine triphosphate (ATP), serotonin (5-HT), acetylcholine (ACh), noradrenaline, histamine, dopamine and glutamate. Why do astrocytes have them, and what are they for? These receptors (GPCRs) raise intracellular calcium concentration by releasing calcium stored within the cells.
Then, do astrocytes release transmitters via synaptic vesicles like neurones, responding to the raised intracellular calcium concentration?
- They do, though such events may not be as major as in neurones; they don’t seem to have an obvious active zone at which dense vesicles accumulate as typically seen in the terminal of pre-synaptic neurones.
- They certainly do: there have been several evidences (1) indicating astrocytes release glutamate in calcium-dependent manner.
Release to where? How would that be useful?
- Astrocytes and neurones are known to form altogether a tripartite synapse comprising pre- and post-synaptic neurones, and peri-synaptic astrocytes. Astrocytes thereto release “gliotransmitter” in support of neurones, as well as protecting them by collecting excess excitatory neurotransmitters.
What on earth is gliotransmitter?
- In the tripartite synapse, astrocytes respond to presynaptic neurones, and release transmitters including glutamate, ATP, prostaglandin E2, and D-serine, in facilitating neuronal activity and synaptic transmission. The term gliotransmitter is used to distinguish the cellular origin of these chemical transmitters at the synapse.
Right, pre-synaptic neurones send signals to astrocytes: is that why the astrocytes have various GPCRs for neurotransmitters?
- I should think so. There is an evidence that exogenous ATP or ACh can increase the astrocytes interconnecting, but not via glutamate (1). Let us move onto see how their interconnection is important, in the next subsection.
Q&A: Gap Junctions and Calcium Oscillation in Astrocytes
Astrocytes can communicate with neighbouring cells by exchanging chemical substances through small gaps between them, known as gap junction. Astrocytes send inter-cellular calcium signalling via gap junctions; by doing that, the signal of calcium oscillation can spread widely across the cells.
Yes, they say that calcium ions propagate waves inside cells and make oscillatory changes. Can you tell us what’s behind the oscillation with a few numbers?
- At resting conditions, intracellular calcium concentration is kept very low, about the ratio of 1:10,000 relative to the extracellular concentration. Upon stimulation, the intracellular concentration is raised by: the release of intracellular storage via certain GPCRs of which action opens IP3 receptors (IP3R) on the endoplasmic reticulum (ER) that stores calcium; and/or by calcium influx via ionotropic channels. The ER also has ryanodine receptor (RyR) which opens at higher calcium concentration. The intracellular calcium concentration is increased from ≈ 0.3 μM until it reaches about 1μM. The activity of phospholiapase C (PLC), which generates IP3, is up-regulated by calcium at its concentration over 100 nM; PLC also activates protein kinase C (PKC) that down regulates PLC. The numbers mentioned here refer to studies on smooth muscle cells (2). The phenomena is IMPOSSIBLE to be described satisfactory in a paragraph….
Let’s not neglect our subject, astrocytes. Is there anything identified to participate in mediating calcium waves in astrocytes?
- Astrocytes need to release ATP when propagating long-range calcium signals. PLC activation causes ATP release from astrocytes (3) and the released ATP to neighbouring cells activates their P2Y receptors (4) which activates PLC, and so it carries on. ATP is an important gliotransmitter between astrocytes through gap junction, as well as at the synaptic cleft between them and neurones.
Let’s carry on talking about another gliotransmitter.
- I’ll mention another one briefly in the next section, with a reference to learning process.
In Learning and Memories: Astrocytes facilitate neuronal transduction
Astrocytes can convert natural L-serine to unnatural D-serine, which is released as a gliotransmitter. D-serine increases calcium permeability of ionotropic glutamate NMDA receptors upon glutamate activation. As mentioned in my previous post (9th.Mar.11), young neurones start responding to glutamate excitatory signal via NMDA receptors with a pronounced responsiveness of long-term potentiation (LTP). These events initiated by calcium propagations do not readily cease, for various intracellular events leading to cellular changes and reorganisation are then processed; calcium signals are thereby crucial in synaptic plasticity, responsible in memory formation.
Oligodendrocytes increases the rate of neuronal conductances
The another type of glial cells, oligodendrocytes are large cells with several elongated protrusions, which can wrap around axon fibres to insulate them with regular intervals: this increases the late of axonal conductance enormously, as well as providing physical protection to the fine axon fibres. A single oligodendrocyte can wrap around (i.e. myelinate) separately each axon extended from a set of neurones that propagate simultaneously; this keeps the integrity of the neuronal activity as this allows neurones to be stay closer as a set of bundles. In this way, oligodendrocytes participate in maintaining coordinated brain networks.
It has been said that learning certain tasks, such as playing a musical instrument, could increase the thickness of the sheath extended from oligodendrocytes; but this might need more verification.
Recently, GPR17, which is a dual receptor for uracil nucleotides and cysteinyl-leukotrienes, was shown to be crucial in the maturation of myelinating oligodendrocytes, and the ligands to the receptor are potential regulators upon them under the normal condition and during myelin repair (5). Oligodendrocytes can also communicate with neurones by means of ATP (6).
Concluding remarks
Glial cells have been underestimated unsung heroes for a very long time. They deserve to be studied more.
R e f e r e n c e s
(1) Several research articles have been published over years by Dr. Philip G. Haydon and co-workers, regarding the function of metabotropic glutamate receptors in astrocytes.
(2) Summarised in a review article by Iino M, 2010. Spatiotemporal dynamics of Ca2+ signaling and its physiological roles. doi:10.2183/pjab.86.244.
(3) Wang Z, Haydon PG, Yeung ES. 2000. Direct observation of calcium-independent intercellular ATP signaling in astrocytes. Analytical Chemistry 72:2001–2007.
(4) Fam SR, Gallagher CJ, Salter MW. 2000. P2Y(1) purinoceptor-mediated Ca(2+) signaling and Ca(2+) wave propagation in dorsal spinal cord astrocytes. The Journal of Neuroscience 20:2800–2808.
(5) Fumagalli M. et al., 2011. J. Biol. Chem. http://www.jbc.org/cgi/doi/10.1074/jbc.M110.162867
(6) Please find several papers published by a group of Dr. R. Douglas Fields.
F u r t h e r R e a d i n g s
Neuroglia, 2nd Ed. Eds. Kettenmann H., Ransom B.R., Oxford Press. 2005.
A lovely book on my wish list. Expensive, but it definitely worths the cost. Beautiful.
The Root of Thought. Koob A. FT Press. 2009.
An affordable popular science book for casual read.
Neural progenitor cells that did not develop into neurones can become glioblasts, which are precursors of astrocytes or oligodendrocytes. These two types of cells are quite different morphologically and functionally; a common factor between the two is primarily to help neurones to function, and to facilitate neurotransmissions.
Astrocytes support neuronal survival and synaptic transmissions
Astrocytes are relatively large cells with sponge-like appearance, extending multiple dendritic protrusions which display finely intricate branching patterns. Astrocytes can be found between blood vessels and neurones, or by synapses.
Basic Role 1: Astrocytes As a Crucial Supplier to Neurones
At blood vessels, astrocytes participate in forming the blood-brain barrier, which selectively takes necessary substances from the circulation into the brain. It sieves out larger and charged molecules sufficiently, but lipophilic substances (e.g. alcohol, synthetic lipid-soluble compounds) that permeate through the cell membranes cannot be excluded by this mechanism; hence such substances elicit central effects.
The blood also carries glutamate, an excitatory neurotransmitter, to the brain. In order to avoid neurones to get excited unnecessarily, neurones do not make a direct contact with the blood vessels. Astrocytes can collect glutamate via glutamate transporters (EAAT1-3) and convert that to a less excitable glutamine.
Glucose, the energy source, is also carried in the blood. Astrocytes collect glucose from the blood using their glucose transporter (GLUT1), and give much of that to energy-intensive neurones after converting it to lactate, which is readily utilisable in ATP synthesis.
Basic Role 2: The Synapses Are Protected by Astrocytes
At synapses, glutamate needs to be removed soon after the transmission, for not only a prolonged excitation cause seizures and paralysis by hyper-activating neurones, an excessive excitation could destroy neurones. The availability of glutamate at synapses therefore needs a close monitoring: astrocytes do this by collecting excess glutamate.
Q&A: G-Protein Couple Receptors and Calcium Oscillation in Astrocytes
The roles of astrocytes mentioned above are important for neurones to function, but the story does not stop there. Astrocytes in fact express various receptors for neurotransmitters including: adenosine triphosphate (ATP), serotonin (5-HT), acetylcholine (ACh), noradrenaline, histamine, dopamine and glutamate. Why do astrocytes have them, and what are they for? These receptors (GPCRs) raise intracellular calcium concentration by releasing calcium stored within the cells.
Then, do astrocytes release transmitters via synaptic vesicles like neurones, responding to the raised intracellular calcium concentration?
- They do, though such events may not be as major as in neurones; they don’t seem to have an obvious active zone at which dense vesicles accumulate as typically seen in the terminal of pre-synaptic neurones.
- They certainly do: there have been several evidences (1) indicating astrocytes release glutamate in calcium-dependent manner.
Release to where? How would that be useful?
- Astrocytes and neurones are known to form altogether a tripartite synapse comprising pre- and post-synaptic neurones, and peri-synaptic astrocytes. Astrocytes thereto release “gliotransmitter” in support of neurones, as well as protecting them by collecting excess excitatory neurotransmitters.
What on earth is gliotransmitter?
- In the tripartite synapse, astrocytes respond to presynaptic neurones, and release transmitters including glutamate, ATP, prostaglandin E2, and D-serine, in facilitating neuronal activity and synaptic transmission. The term gliotransmitter is used to distinguish the cellular origin of these chemical transmitters at the synapse.
Right, pre-synaptic neurones send signals to astrocytes: is that why the astrocytes have various GPCRs for neurotransmitters?
- I should think so. There is an evidence that exogenous ATP or ACh can increase the astrocytes interconnecting, but not via glutamate (1). Let us move onto see how their interconnection is important, in the next subsection.
Q&A: Gap Junctions and Calcium Oscillation in Astrocytes
Astrocytes can communicate with neighbouring cells by exchanging chemical substances through small gaps between them, known as gap junction. Astrocytes send inter-cellular calcium signalling via gap junctions; by doing that, the signal of calcium oscillation can spread widely across the cells.
Yes, they say that calcium ions propagate waves inside cells and make oscillatory changes. Can you tell us what’s behind the oscillation with a few numbers?
- At resting conditions, intracellular calcium concentration is kept very low, about the ratio of 1:10,000 relative to the extracellular concentration. Upon stimulation, the intracellular concentration is raised by: the release of intracellular storage via certain GPCRs of which action opens IP3 receptors (IP3R) on the endoplasmic reticulum (ER) that stores calcium; and/or by calcium influx via ionotropic channels. The ER also has ryanodine receptor (RyR) which opens at higher calcium concentration. The intracellular calcium concentration is increased from ≈ 0.3 μM until it reaches about 1μM. The activity of phospholiapase C (PLC), which generates IP3, is up-regulated by calcium at its concentration over 100 nM; PLC also activates protein kinase C (PKC) that down regulates PLC. The numbers mentioned here refer to studies on smooth muscle cells (2). The phenomena is IMPOSSIBLE to be described satisfactory in a paragraph….
Let’s not neglect our subject, astrocytes. Is there anything identified to participate in mediating calcium waves in astrocytes?
- Astrocytes need to release ATP when propagating long-range calcium signals. PLC activation causes ATP release from astrocytes (3) and the released ATP to neighbouring cells activates their P2Y receptors (4) which activates PLC, and so it carries on. ATP is an important gliotransmitter between astrocytes through gap junction, as well as at the synaptic cleft between them and neurones.
Let’s carry on talking about another gliotransmitter.
- I’ll mention another one briefly in the next section, with a reference to learning process.
In Learning and Memories: Astrocytes facilitate neuronal transduction
Astrocytes can convert natural L-serine to unnatural D-serine, which is released as a gliotransmitter. D-serine increases calcium permeability of ionotropic glutamate NMDA receptors upon glutamate activation. As mentioned in my previous post (9th.Mar.11), young neurones start responding to glutamate excitatory signal via NMDA receptors with a pronounced responsiveness of long-term potentiation (LTP). These events initiated by calcium propagations do not readily cease, for various intracellular events leading to cellular changes and reorganisation are then processed; calcium signals are thereby crucial in synaptic plasticity, responsible in memory formation.
Oligodendrocytes increases the rate of neuronal conductances
The another type of glial cells, oligodendrocytes are large cells with several elongated protrusions, which can wrap around axon fibres to insulate them with regular intervals: this increases the late of axonal conductance enormously, as well as providing physical protection to the fine axon fibres. A single oligodendrocyte can wrap around (i.e. myelinate) separately each axon extended from a set of neurones that propagate simultaneously; this keeps the integrity of the neuronal activity as this allows neurones to be stay closer as a set of bundles. In this way, oligodendrocytes participate in maintaining coordinated brain networks.
It has been said that learning certain tasks, such as playing a musical instrument, could increase the thickness of the sheath extended from oligodendrocytes; but this might need more verification.
Recently, GPR17, which is a dual receptor for uracil nucleotides and cysteinyl-leukotrienes, was shown to be crucial in the maturation of myelinating oligodendrocytes, and the ligands to the receptor are potential regulators upon them under the normal condition and during myelin repair (5). Oligodendrocytes can also communicate with neurones by means of ATP (6).
Concluding remarks
Glial cells have been underestimated unsung heroes for a very long time. They deserve to be studied more.
R e f e r e n c e s
(1) Several research articles have been published over years by Dr. Philip G. Haydon and co-workers, regarding the function of metabotropic glutamate receptors in astrocytes.
(2) Summarised in a review article by Iino M, 2010. Spatiotemporal dynamics of Ca2+ signaling and its physiological roles. doi:10.2183/pjab.86.244.
(3) Wang Z, Haydon PG, Yeung ES. 2000. Direct observation of calcium-independent intercellular ATP signaling in astrocytes. Analytical Chemistry 72:2001–2007.
(4) Fam SR, Gallagher CJ, Salter MW. 2000. P2Y(1) purinoceptor-mediated Ca(2+) signaling and Ca(2+) wave propagation in dorsal spinal cord astrocytes. The Journal of Neuroscience 20:2800–2808.
(5) Fumagalli M. et al., 2011. J. Biol. Chem. http://www.jbc.org/cgi/doi/10.1074/jbc.M110.162867
(6) Please find several papers published by a group of Dr. R. Douglas Fields.
F u r t h e r R e a d i n g s
Neuroglia, 2nd Ed. Eds. Kettenmann H., Ransom B.R., Oxford Press. 2005.
A lovely book on my wish list. Expensive, but it definitely worths the cost. Beautiful.
The Root of Thought. Koob A. FT Press. 2009.
An affordable popular science book for casual read.
Friday, 4 March 2011
Thoughts on Dual Linguistic Processing and What Could Affect Neurogenesis in Ageing Brain
Learning to do a unfamiliar task may seem like a time-consuming process at first, taking much time away. As soon as taking a hold of it, however, we could be gripped by a feeling of excitement start rushing in. I presume it could be the moment at which the newly established neural connections have been recognised in one head.
To provide an example to illustrate, I describe my recent struggle with translating a few writings from one language to another. At first I did not enjoy the activity, mainly for overwhelming fuzzy uncertainty. Although it still bothers me when precisions in semantics are sought in detail, nevertheless I became less frustrated as I got faster at the task; the “fuzziness” also turned from mere messy confusions into compromises upon predicting applicability of logic.
The uncomfortableness I experienced is thought to be due to the fact that I had rarely attempted to use two languages simultaneously. One language often predominates another as one is used to receive, think and express, applying a set of rules at each occasion. Interchanging two sets of the rules is like travelling between two distinct entities processing same information differently. That is because the differences between languages often are not only lexical semantics and grammatical structures, there is a semi-subliminal differences in cultural norms underlining beneath at places. The separate entities could be kept apart in a brain. The distance though, appeared to have shrunk as I practiced more; the process gradually speeded up, until eventually the two sets became more like a two-sided card which could be turned around at ease.
With my irrepressible tendency to speculate, I could hardly resist to propose that there must have been some sort of structural changes occurring at the area governing language processing, possibly by means of:
1) establishing new connections associating the two sets for quicker access to each or both simultaneously;
2) extending existing neuronal connections between the two sets of information to allow direct comparisons and mirroring of information in the two sets; or
3) strengthening already existing connections between the two to increase the speed of communications.
The first two possibilities above would involve neuroanatomical changes by synaptic re-configurations, and as for the third, it can be done by increasing glial cells (oligodendrocytes) which wrap around the axons to increase the electrical conductivity by insulating.
Before I get carried away full blowing the speculations on multilingual processing in cerebrum, saving that to another occasion, I should better move on to focus on the process generating neuronal cells from progenitor cells (i.e. neurogenesis) in mature mammalian brains. Neural progenitor cells can divide into neurones or glial cells (astrocytes or oligodendrocytes). In the following section, the development of neurones in adult rodents is summarised.
Neurogenesis in the dentate gyrus by the hippocampus contribute to the learning in adulthood
Leaning tasks and memory acquisition involve neural re-configuration. A study evaluated cell proliferation in the hippocampus and the medial prefrontal cortex during and after learning revealed that increased number of newborn neurones were observed during learning (Rapanelli, Frick and Zanutto, 2011).
In a mature mammalian brain, neurones can be formed from neural progenitor cells in two regions: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus (DG). Newly made neurones in the former migrate to the olfactory bulb, and the newborns in the latter integrate locally into the neural circuitry of the DG (reviewed by Deng, Aimone and Gage, 2010). The following describes the latter event.
The newly born, small neurones (granule cells) in the DG often retain a high intracellular chloride concentration due to the activity of Na-K-2Cl cation-anion co-transporter, NKCC1, which imports chloride. The cells are under the influence of neighbouring cells releasing gamma-aminobutyric acid (GABA) (i.e. GABAergic neurones); the GABAergic input, which has an inhibitory effect on mature neurones, can exhibit a tonic excitatory effect on the granule cells, as the opening of ionotropic GABAA receptor causes chloride efflux by the concentration gradient (reviewed by Ben-Ari. et al. 2007).
Gradually, the granule cells start forming extended synapses with pyramidal neurones in cornu Ammonis 3 (CA3) area within the hippocampus; some connect with the perforant path of axons extended from the entorhinal cortex of rhinal cortical area, which functions as an interface between the hippocampus and the neocortex. The newly integrated connections involves glutamatergic output, and the granule cells start responding to it primarily via N-methyl-D-Aspartate (NMDA) receptors which flux calcium. At this stage, the action of GABAergic input becomes inhibitory as the expression of a K-Cl co-transporter KCC, which exports chloride, becomes more prominent. The inhibitory effect of GABA on maturing neurones is also increased by the action of metabotropic GABAB receptor, which contributes to hyperpolarisation by activating inward-rectifying potassium channel (Kir). For a while, these cells display stronger synaptic plasticity with lower threshold for inducing long-term potentiation (LTP) with higher amplitudes. LTP induced between the perforant path and granule cells was demonstrated to increase survival of newborn cells (Bruel-Jungerman et al., 2006). The developing period of the cells (up to 6 weeks in rodents) appear to contribute to memory formation in adult (reviewed by Deng, Aimone and Gage, 2010).
Not only mental, but physical exercises could also increase neurogenesis
There have been evidences indicating that physical exercises also improve the number of granule cells in the dentate gyrus in rodents, as well as improving cognition in humans. The induction of angiogenesis and expression of neurotrophic factors have been the likely reasons for the positive effect of exercises (reviewed by Deng, Aimone and Gage, 2010).
In addition to glutamate and GABA, a few neurotransmitters have been suggested to participate in the proliferation of neural progenitor cells upon exercises, as summarised below. However, the direct effects of these on adult neurogenesis remain yet largely uncertain.
Beta-endorphin
The loss of neurogenesis in neurological conditions
The process of neurogenesis is negatively affected in conditions with notable cognitive decline, including major depression and neurodegenerative diseases such as Alzheimer’s disease (reviewed by Zhao, Deng and Gage 2008; Mattson 2008). Approaches to restore neurogenesis might be beneficial for patients affected by these conditions, whilst efforts of sustaining neurogenesis may provide preventative measures.
References
Ben-Ari Y. et al., 2007. GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations. Physiol. Rev. 87: 1215-1284.
Bruel-Jungerman E. et al., 2006. Long-Term Potentiation Enhances Neurogenesis in the Adult Dentate Gyrus. The Journal of Neuroscience 26: 5888 –5893.
Deng W., Aimone J.B. & Gage F.H. 2010. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat. Rev. Neurosci. 11: 339–350.
Koehl M. et al., 2008. Exercise-induced promotion of hippocampal cell proliferation requires β-endorphin. FASEB 22: 2253-2262.
Kotani S. et al., 2006. Pharmacological evidence of cholinergic involvement in adult hippocampal neurogenesis in rats. Neuroscience 142: 505-514.
Mattson M.P. 2008. Glutamate and Neurotrophic Factors in Neuronal Plasticity and Disease. Ann. N. Y. Acad. Sci. 1144: 97–112.
Persson, A.I. et al., 2003. Opioid-induced proliferation through the MAPK pathway in cultures of adult hippocampal progenitors. Mol. Cell. Neurosci. 23: 360-372.
Rapanelli M., Frick L.R. & Zanutto B.S., 2011. Learning an Operant Conditioning Task Differentially Induces Gliogenesis in the Medial Prefrontal Cortex and Neurogenesis in the Hippocampus. PLoS ONE 6: e14713.
Resende P.R. & Adhikari A., 2009. Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation. Cell Communication and Signaling. 7: 20 BioMed Central.
Rizk P. et al., 2006. The alpha2-adrenoceptor antagonist dexefaroxan enhances hippocampal neurogenesis by increasing the survival and differentiation of new granule cells. Neuropsychopharmacology 31: 1146-1157.
Raynor K. et al., 1994. Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol. Pharmacol. 45: 330-334.
Simonin F. et al., 1995. K-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system. Proc. Natl. Acad. Sci. U S A, 92: 7006-7010.
Toll L. et al., 1998. Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res. Monogr. 178: 440-466.
Yasuda K. et al., 1993. Cloning and functional comparison of κ and δ opioid receptors from mouse brain. Proc. Natl. Acad. Sci. USA, 90: 6736-6740.
Zhao C., Deng W., & Gage F.H. 2008. Mechanisms and functional implications of adult neurogenesis. Cell 132: 645–660.
Zhang H. et al., 2006. Endogenous opioids upregulate brain-derived neurotrophic factor mRNA through delta- and micro-opioid receptors independent of antidepressant-like effects. Eur. J. Neurosci. 23: 984–994.
To provide an example to illustrate, I describe my recent struggle with translating a few writings from one language to another. At first I did not enjoy the activity, mainly for overwhelming fuzzy uncertainty. Although it still bothers me when precisions in semantics are sought in detail, nevertheless I became less frustrated as I got faster at the task; the “fuzziness” also turned from mere messy confusions into compromises upon predicting applicability of logic.
The uncomfortableness I experienced is thought to be due to the fact that I had rarely attempted to use two languages simultaneously. One language often predominates another as one is used to receive, think and express, applying a set of rules at each occasion. Interchanging two sets of the rules is like travelling between two distinct entities processing same information differently. That is because the differences between languages often are not only lexical semantics and grammatical structures, there is a semi-subliminal differences in cultural norms underlining beneath at places. The separate entities could be kept apart in a brain. The distance though, appeared to have shrunk as I practiced more; the process gradually speeded up, until eventually the two sets became more like a two-sided card which could be turned around at ease.
With my irrepressible tendency to speculate, I could hardly resist to propose that there must have been some sort of structural changes occurring at the area governing language processing, possibly by means of:
1) establishing new connections associating the two sets for quicker access to each or both simultaneously;
2) extending existing neuronal connections between the two sets of information to allow direct comparisons and mirroring of information in the two sets; or
3) strengthening already existing connections between the two to increase the speed of communications.
The first two possibilities above would involve neuroanatomical changes by synaptic re-configurations, and as for the third, it can be done by increasing glial cells (oligodendrocytes) which wrap around the axons to increase the electrical conductivity by insulating.
Before I get carried away full blowing the speculations on multilingual processing in cerebrum, saving that to another occasion, I should better move on to focus on the process generating neuronal cells from progenitor cells (i.e. neurogenesis) in mature mammalian brains. Neural progenitor cells can divide into neurones or glial cells (astrocytes or oligodendrocytes). In the following section, the development of neurones in adult rodents is summarised.
Neurogenesis in the dentate gyrus by the hippocampus contribute to the learning in adulthood
Leaning tasks and memory acquisition involve neural re-configuration. A study evaluated cell proliferation in the hippocampus and the medial prefrontal cortex during and after learning revealed that increased number of newborn neurones were observed during learning (Rapanelli, Frick and Zanutto, 2011).
In a mature mammalian brain, neurones can be formed from neural progenitor cells in two regions: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus (DG). Newly made neurones in the former migrate to the olfactory bulb, and the newborns in the latter integrate locally into the neural circuitry of the DG (reviewed by Deng, Aimone and Gage, 2010). The following describes the latter event.
The newly born, small neurones (granule cells) in the DG often retain a high intracellular chloride concentration due to the activity of Na-K-2Cl cation-anion co-transporter, NKCC1, which imports chloride. The cells are under the influence of neighbouring cells releasing gamma-aminobutyric acid (GABA) (i.e. GABAergic neurones); the GABAergic input, which has an inhibitory effect on mature neurones, can exhibit a tonic excitatory effect on the granule cells, as the opening of ionotropic GABAA receptor causes chloride efflux by the concentration gradient (reviewed by Ben-Ari. et al. 2007).
Gradually, the granule cells start forming extended synapses with pyramidal neurones in cornu Ammonis 3 (CA3) area within the hippocampus; some connect with the perforant path of axons extended from the entorhinal cortex of rhinal cortical area, which functions as an interface between the hippocampus and the neocortex. The newly integrated connections involves glutamatergic output, and the granule cells start responding to it primarily via N-methyl-D-Aspartate (NMDA) receptors which flux calcium. At this stage, the action of GABAergic input becomes inhibitory as the expression of a K-Cl co-transporter KCC, which exports chloride, becomes more prominent. The inhibitory effect of GABA on maturing neurones is also increased by the action of metabotropic GABAB receptor, which contributes to hyperpolarisation by activating inward-rectifying potassium channel (Kir). For a while, these cells display stronger synaptic plasticity with lower threshold for inducing long-term potentiation (LTP) with higher amplitudes. LTP induced between the perforant path and granule cells was demonstrated to increase survival of newborn cells (Bruel-Jungerman et al., 2006). The developing period of the cells (up to 6 weeks in rodents) appear to contribute to memory formation in adult (reviewed by Deng, Aimone and Gage, 2010).
Not only mental, but physical exercises could also increase neurogenesis
There have been evidences indicating that physical exercises also improve the number of granule cells in the dentate gyrus in rodents, as well as improving cognition in humans. The induction of angiogenesis and expression of neurotrophic factors have been the likely reasons for the positive effect of exercises (reviewed by Deng, Aimone and Gage, 2010).
In addition to glutamate and GABA, a few neurotransmitters have been suggested to participate in the proliferation of neural progenitor cells upon exercises, as summarised below. However, the direct effects of these on adult neurogenesis remain yet largely uncertain.
Beta-endorphin
Physical exercises are known to stimulate the releases of β-endorphin, which elicits full effects at μ receptors and also at δ receptors (Raynor et al., 1994; Toll et al., 1998), or just partial effect at κ receptors (Simonin et al., 1995; Yasuda et al., 1993). Rat hippocampal progenitor cells are shown to proliferate more after β-endorphin treatment, and the proliferative effect was reversed by a μ antagonist naloxone (Persson et al., 2003). A knockout study wherein the effect of missing β-endorphin was investigated in mice showed that the proliferative effect, induced by physical exercise, decreased during the developing stage up to the 5th week of neurogenesis in the absence of β-endorphin (Koehl et al., 2008). Endogenous opioids including β-endorphin and enkephalins have been shown to up-regulate brain-derived neurotrophic factor (BDNF) notably in the DG (Zhang et al., 2006); this could be a reason contributing to the proliferative effect of β-endorphin on neural progenitor cells.
Acetylcholine
The four weeks treatment of adult rats with an acetylcholinesterase inhibitor donepezil was reported to increase proliferative cells in the dentate gyrus, and a same-length treatment with muscarinic acetylcholine receptor antagonist scopolamine showed the opposite effect. The study also revealed that the expression of phosphorylated cAMP response element binding protein (CREB) was enhanced by the former treatment whilst it was suppressed by the latter (Kotani et al., 2006). The positive actions of both muscarinic and nicotinic receptors on cell proliferation and neural differentiation, largely by increasing intracellular calcium concentration, have been documented (reviewed by Resende and Adhikari, 2009).
Noradrenaline
A selective antagonist dexefaroxan inhibits alpha2-adrenoceptor, which is a presynaptic inhibitory autoreceptor for the noradrenaline release in the hippocampus. Although prolonged systemic treatment of rats with dexefaroxan did not affect neurogenesis in dentate gyrus, it was shown to promote survival of newborns (Rizk et al., 2006).
The loss of neurogenesis in neurological conditions
The process of neurogenesis is negatively affected in conditions with notable cognitive decline, including major depression and neurodegenerative diseases such as Alzheimer’s disease (reviewed by Zhao, Deng and Gage 2008; Mattson 2008). Approaches to restore neurogenesis might be beneficial for patients affected by these conditions, whilst efforts of sustaining neurogenesis may provide preventative measures.
References
Ben-Ari Y. et al., 2007. GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations. Physiol. Rev. 87: 1215-1284.
Bruel-Jungerman E. et al., 2006. Long-Term Potentiation Enhances Neurogenesis in the Adult Dentate Gyrus. The Journal of Neuroscience 26: 5888 –5893.
Deng W., Aimone J.B. & Gage F.H. 2010. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat. Rev. Neurosci. 11: 339–350.
Koehl M. et al., 2008. Exercise-induced promotion of hippocampal cell proliferation requires β-endorphin. FASEB 22: 2253-2262.
Kotani S. et al., 2006. Pharmacological evidence of cholinergic involvement in adult hippocampal neurogenesis in rats. Neuroscience 142: 505-514.
Mattson M.P. 2008. Glutamate and Neurotrophic Factors in Neuronal Plasticity and Disease. Ann. N. Y. Acad. Sci. 1144: 97–112.
Persson, A.I. et al., 2003. Opioid-induced proliferation through the MAPK pathway in cultures of adult hippocampal progenitors. Mol. Cell. Neurosci. 23: 360-372.
Rapanelli M., Frick L.R. & Zanutto B.S., 2011. Learning an Operant Conditioning Task Differentially Induces Gliogenesis in the Medial Prefrontal Cortex and Neurogenesis in the Hippocampus. PLoS ONE 6: e14713.
Resende P.R. & Adhikari A., 2009. Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation. Cell Communication and Signaling. 7: 20 BioMed Central.
Rizk P. et al., 2006. The alpha2-adrenoceptor antagonist dexefaroxan enhances hippocampal neurogenesis by increasing the survival and differentiation of new granule cells. Neuropsychopharmacology 31: 1146-1157.
Raynor K. et al., 1994. Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol. Pharmacol. 45: 330-334.
Simonin F. et al., 1995. K-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system. Proc. Natl. Acad. Sci. U S A, 92: 7006-7010.
Toll L. et al., 1998. Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res. Monogr. 178: 440-466.
Yasuda K. et al., 1993. Cloning and functional comparison of κ and δ opioid receptors from mouse brain. Proc. Natl. Acad. Sci. USA, 90: 6736-6740.
Zhao C., Deng W., & Gage F.H. 2008. Mechanisms and functional implications of adult neurogenesis. Cell 132: 645–660.
Zhang H. et al., 2006. Endogenous opioids upregulate brain-derived neurotrophic factor mRNA through delta- and micro-opioid receptors independent of antidepressant-like effects. Eur. J. Neurosci. 23: 984–994.
Monday, 14 February 2011
The Neurochemistry of monoamines and the Work Efficiency (and its implication on affective conditions)
A job could be auspicious when it matches motives
I would like to start writing this by describing my recent experience in job-hunting.
After a pile of unsuccessful job applications, I was called for an interview at last, for a position of technical translator. I am a novice to translation jobs; so no work has yet been promised but I was given an opportunity to prove that I qualify to meet the demand by sufficiently translating a few test materials given. The subjects were unfamiliar and unrelated to my interests, and so I have been attempting to read around, to get some relevant background information.
Minor intellectual challenges associated with it allowed me going on for a short while, but I soon found it tiring to maintain focus on topics that do not interests me. Somehow disproportionally exhausted, I was left with a sinking feeling when the attempts of translating made me feel as if I am turning into some kind of an automaton. More than anything I missed the subjects familiar to me; then I had to revisit my usual playground of biological sciences to make myself feel human again.
Reading, on the subjects that fascinates one, is a completely different experience. The joyful process seems endless as always there will be new questions of which answers need to be searched for. In the iterative processes of search, retrieval, and organising, I could easily lose myself and forget the rest. As all the excitements somehow seem to cancel out any fatigue, the activity could easily be carried out as long as that takes if circumstances allow me to do so.
Clearly, there is a fine coordinated biochemistry happening then, to mesmerise one into the activity. I propose the culprits here to be three monoamines: serotonin, dopamine and noradrenaline. In a minimal explanation, serotonin and dopamine bring the feeling of being rewarded and content, and noradrenaline helps maintaining focus and alertness at right doses.
Three monoamines: serotonin, dopamine and noradrenaline
5-hydroxytryptamine (5-HT: serotonin), dopamine (DA), and noradrenaline (NA), are neurotransmitters biosynthesised from amino acids tryptophan, phenylalanine or tyrosine. Appropriate hydroxylation and decarboxylation of tryptophan yields 5-HT, whilst that of tyrosine makes DA, which becomes NE via another hydroxylation.
The synthesis is regulated by the end-product inhibition, meaning the specific enzymatic activity (of hydroxylase etc.) is reduced by high cytosolic concentration of the product in the axon terminal whilst these are stored. When monoamines are released promptly, the elevated intracellular calcium concentration (as a result of transmitter release) up-regulates the enzyme to restock the transmitters.
5-HT (serotonin)
5-HT is generally associated with positive effects on mood conditions. Several agents are currently available to treat acute depression by increasing the synaptic availability of 5-HT; but the therapeutic efficacy of these compounds, selective-serotonin re-uptake inhibitors (SSRIs), may not actually be that great (Kirsch et al., 2008). The rapid increase in SSRI sales did not significantly decrease the suicide rates in four Nordic countries in an overall trend between the early 90s and 2006, though whether the committed were on the medication remains unknown (Zahl et al., 2010); someone with no hope but a death wish may unlikely visit a doctor. In addition to the positive affective effects, 5-HT has a property of emesis induction by acting on its ionotropic receptor.
DA (dopamine)
DA is well-known for its role in what perceived as rewarding or motivating, as dopaminergic neurones in the ventral tegmental area of the midbrain release DA to the basal forebrain area (i.e. the mesocorticolimbic dopamine system). The downside of the system manifests when the reinforcing tendency turns into an addiction. That could happen in responses to stimuli which raises DA at the synapses. For instances, opioids and nicotine stimulate DA release as the dopaminergic neurones have opioid receptors and nicotinic acetylcholine receptors, and cocaine prolong DA availability by preventing its re-uptake at the terminal notably in the nucleus accumbens.
(NA) Noradrenaline
NA has several roles in both central and peripheral systems.
At synapses, it limits excitatory transmission by glutamate (Scheiderer et al. 2003; 2008). The peripheral action of NA could increase alertness, startle response and decrease sleep.
The restoring fine balance in the co-existing three might be more helpful than simply interfering with one of them
Currently, affective disorders such as depressions are often dealt with SSRI prescription. But, as mentioned above, the effectiveness of the treatment has been questioned. That might suggest that an artificial up-regulation of a single neurotransmitter may not be appropriate or sufficient to restore motivations, aspirations, and willingness: the missing components in the affective condition like major depression. There have been recent developments in the triple re-uptake inhibitor of the three monoamines (Caldarone et al., 2010, Nathan et al., 2010; Prins et al., 20011; Shao et al., 2011). In future such compounds might possibly provide an effective treatment for those in desperate needs when administered carefully; however, individual tendencies and plausible genetic susceptibility towards relevant conditions (e.g. addictions, substance misuse etc.) must be taken into account.
What makes one attaches to certain specific subjects and why?
I vaguely ponder of the questions and relate that to our innate curiosity and craving for understanding unknowns. It could merely be that we all enjoy doing what we are capable of reasonably well-comprehending. The nature of specificity, how various subjects are selected by a range of individuals, appears largely diverse. Undoubtedly, these variations in the brain structure and chemistry allowed humans to develop extensively to live in the societies with multi-functional features. We should better appreciate all individual differences existing therein.
An attempt to discuss these three neurotransmitters from a different perspective would be made in another opportunity sometime.
References
Caldarone BJ. et al., 2010. The novel triple reuptake inhibitor JZAD-IV-22 exhibits an antidepressant pharmacological profile without locomotor stimulant or sensitization properties. J Pharmacol Exp Ther 335(3):762-70. (NOT open access)
Kirsch I. et al., 2008. Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration. PLoS Medicine 5(2) e.45.
Nathan PJ. et al., 2010. Neuropsychiatric Adverse Effects of Centrally Acting Antiobesity Drugs. CNS Neurosci Ther (NOT accessible: abstract viewable at Entrez pubmed).
Prins J. et al., 2011.The potential and limitations of DOV 216,303 as a triple reuptake inhibitor for the treatment of major depression: a microdialysis study in olfactory bulbectomized rats. Pharmacol Biochem Behav 97(3):444-52.
Scheiderer CL, Dobrunz LE, and McMahan LL, 2003. Novel Form of Long-Term Synaptic Depression in Rat Hippocampus Induced By Activation of alpha1 Adrenergic Receptors. J Neurophysiol 91:1071–1077.
Scheiderer CL et al., 2008. Coactivation of M(1) muscarinic and alpha1 adrenergic receptors stimulates extracellular signal-regulated protein kinase and induces long-term depression at CA3-CA1 synapses in rat hippocampus. J Neurosci 28:5350–5358.
Shao L. et al., 2011. Discovery of N-methyl-1-(1-phenylcyclohexyl)ethanamine, a novel triple serotonin, norepinephrine and dopamine reuptake inhibitor. Bioorg Med Chem Lett.
Zahl PH et al., 2010. The relationship between sales of SSRI, TCA and suicide rates in the Nordic countries. BMC Psychiatry, 10:62.
I would like to start writing this by describing my recent experience in job-hunting.
After a pile of unsuccessful job applications, I was called for an interview at last, for a position of technical translator. I am a novice to translation jobs; so no work has yet been promised but I was given an opportunity to prove that I qualify to meet the demand by sufficiently translating a few test materials given. The subjects were unfamiliar and unrelated to my interests, and so I have been attempting to read around, to get some relevant background information.
Minor intellectual challenges associated with it allowed me going on for a short while, but I soon found it tiring to maintain focus on topics that do not interests me. Somehow disproportionally exhausted, I was left with a sinking feeling when the attempts of translating made me feel as if I am turning into some kind of an automaton. More than anything I missed the subjects familiar to me; then I had to revisit my usual playground of biological sciences to make myself feel human again.
Reading, on the subjects that fascinates one, is a completely different experience. The joyful process seems endless as always there will be new questions of which answers need to be searched for. In the iterative processes of search, retrieval, and organising, I could easily lose myself and forget the rest. As all the excitements somehow seem to cancel out any fatigue, the activity could easily be carried out as long as that takes if circumstances allow me to do so.
Clearly, there is a fine coordinated biochemistry happening then, to mesmerise one into the activity. I propose the culprits here to be three monoamines: serotonin, dopamine and noradrenaline. In a minimal explanation, serotonin and dopamine bring the feeling of being rewarded and content, and noradrenaline helps maintaining focus and alertness at right doses.
Three monoamines: serotonin, dopamine and noradrenaline
5-hydroxytryptamine (5-HT: serotonin), dopamine (DA), and noradrenaline (NA), are neurotransmitters biosynthesised from amino acids tryptophan, phenylalanine or tyrosine. Appropriate hydroxylation and decarboxylation of tryptophan yields 5-HT, whilst that of tyrosine makes DA, which becomes NE via another hydroxylation.
The synthesis is regulated by the end-product inhibition, meaning the specific enzymatic activity (of hydroxylase etc.) is reduced by high cytosolic concentration of the product in the axon terminal whilst these are stored. When monoamines are released promptly, the elevated intracellular calcium concentration (as a result of transmitter release) up-regulates the enzyme to restock the transmitters.
5-HT (serotonin)
5-HT is generally associated with positive effects on mood conditions. Several agents are currently available to treat acute depression by increasing the synaptic availability of 5-HT; but the therapeutic efficacy of these compounds, selective-serotonin re-uptake inhibitors (SSRIs), may not actually be that great (Kirsch et al., 2008). The rapid increase in SSRI sales did not significantly decrease the suicide rates in four Nordic countries in an overall trend between the early 90s and 2006, though whether the committed were on the medication remains unknown (Zahl et al., 2010); someone with no hope but a death wish may unlikely visit a doctor. In addition to the positive affective effects, 5-HT has a property of emesis induction by acting on its ionotropic receptor.
DA (dopamine)
DA is well-known for its role in what perceived as rewarding or motivating, as dopaminergic neurones in the ventral tegmental area of the midbrain release DA to the basal forebrain area (i.e. the mesocorticolimbic dopamine system). The downside of the system manifests when the reinforcing tendency turns into an addiction. That could happen in responses to stimuli which raises DA at the synapses. For instances, opioids and nicotine stimulate DA release as the dopaminergic neurones have opioid receptors and nicotinic acetylcholine receptors, and cocaine prolong DA availability by preventing its re-uptake at the terminal notably in the nucleus accumbens.
(NA) Noradrenaline
NA has several roles in both central and peripheral systems.
At synapses, it limits excitatory transmission by glutamate (Scheiderer et al. 2003; 2008). The peripheral action of NA could increase alertness, startle response and decrease sleep.
The restoring fine balance in the co-existing three might be more helpful than simply interfering with one of them
Currently, affective disorders such as depressions are often dealt with SSRI prescription. But, as mentioned above, the effectiveness of the treatment has been questioned. That might suggest that an artificial up-regulation of a single neurotransmitter may not be appropriate or sufficient to restore motivations, aspirations, and willingness: the missing components in the affective condition like major depression. There have been recent developments in the triple re-uptake inhibitor of the three monoamines (Caldarone et al., 2010, Nathan et al., 2010; Prins et al., 20011; Shao et al., 2011). In future such compounds might possibly provide an effective treatment for those in desperate needs when administered carefully; however, individual tendencies and plausible genetic susceptibility towards relevant conditions (e.g. addictions, substance misuse etc.) must be taken into account.
What makes one attaches to certain specific subjects and why?
I vaguely ponder of the questions and relate that to our innate curiosity and craving for understanding unknowns. It could merely be that we all enjoy doing what we are capable of reasonably well-comprehending. The nature of specificity, how various subjects are selected by a range of individuals, appears largely diverse. Undoubtedly, these variations in the brain structure and chemistry allowed humans to develop extensively to live in the societies with multi-functional features. We should better appreciate all individual differences existing therein.
An attempt to discuss these three neurotransmitters from a different perspective would be made in another opportunity sometime.
References
Caldarone BJ. et al., 2010. The novel triple reuptake inhibitor JZAD-IV-22 exhibits an antidepressant pharmacological profile without locomotor stimulant or sensitization properties. J Pharmacol Exp Ther 335(3):762-70. (NOT open access)
Kirsch I. et al., 2008. Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration. PLoS Medicine 5(2) e.45.
Nathan PJ. et al., 2010. Neuropsychiatric Adverse Effects of Centrally Acting Antiobesity Drugs. CNS Neurosci Ther (NOT accessible: abstract viewable at Entrez pubmed).
Prins J. et al., 2011.The potential and limitations of DOV 216,303 as a triple reuptake inhibitor for the treatment of major depression: a microdialysis study in olfactory bulbectomized rats. Pharmacol Biochem Behav 97(3):444-52.
Scheiderer CL, Dobrunz LE, and McMahan LL, 2003. Novel Form of Long-Term Synaptic Depression in Rat Hippocampus Induced By Activation of alpha1 Adrenergic Receptors. J Neurophysiol 91:1071–1077.
Scheiderer CL et al., 2008. Coactivation of M(1) muscarinic and alpha1 adrenergic receptors stimulates extracellular signal-regulated protein kinase and induces long-term depression at CA3-CA1 synapses in rat hippocampus. J Neurosci 28:5350–5358.
Shao L. et al., 2011. Discovery of N-methyl-1-(1-phenylcyclohexyl)ethanamine, a novel triple serotonin, norepinephrine and dopamine reuptake inhibitor. Bioorg Med Chem Lett.
Zahl PH et al., 2010. The relationship between sales of SSRI, TCA and suicide rates in the Nordic countries. BMC Psychiatry, 10:62.
Friday, 14 January 2011
Two Short Writings on Suicide: At the Edges and the Snow-White’s Apple
I. A view on attempted suicides
This thread is written based on a string of thoughts on life and suicide, which was first initiated by encountering an epidemiological study published last year:
Psychosis alters association between IQ and future risk of attempted suicide: cohort study of 1 109 475 Swedish men
Batty GD, Whitley E, Deary IJ, Gale CR, Tynelius P, Rasmussen F, 2010. BMJ 340: c2506
The study concluded: Low IQ scores in early adulthood were associated with a subsequently increased risk of attempted suicide in men free from psychosis. A greater understanding of the mechanisms underlying these associations may provide opportunities and strategies for prevention.
I would like to expand the issue of attempted suicide beyond mere ineptness due to the lack of clear planning, though I should not totally exclude this possibility.
Low Intelligence Quotient scores may reflect their tendency to be driven emotionally
Individuals with low IQ scores are likely to under-perform academically and perhaps being short of a logic-based problem solving skill. Frustrated bullies at schools might belong to this category; one may find it hard to have an in-depth rational conversation with a bully, that is because their actions are often driven by emotions which inhibit coherent thinking process. The emotional inhibition of logical thinking might also contribute to their underperformance in IQ tests to some extent, for their negative emotions associated with being assessed in general; having lower self-esteem would be a contributing factor makes them susceptible to such effects.
Other possible measure in speculation
Even if individuals with low IQ scores do have deficits in the aspects of cognitive intelligence regardless of their emotional status, the majority (96% of the lowest IQ group in the study above) do not attempt suicide and may live quite happy life. One would speculate that there might be compensatory skills which make them suited to live in human society despite the deficit.
The idea of EQ (empathy quotient) has been introduced by Baron-Cohen as a measure of an ability to grasp others’ emotions and intentions by “social cues” given by facial expressions etc; EQ is a prerequisite for social skills, and low EQ is associated with higher functioning autism-spectrum condition with normal or above intelligence (Baron-Cohen and Wheelwright, 2004). The individuals with high EQ are regarded as being sympathetic in understanding the pains which others may feel; they likely are towards friends they love, but possibly less to enemies they disrespect or feel threatened by (evidently seen in human histories of wars and crimes). The individuals operate comfortably within a group are always quick to suss out the deviates of the group; low IQ with high EQ could altogether devalue and exclude high IQ with low EQ when the former failed to fully understand and acknowledge the latter and vice versa - it might appear slightly off-the-topic, but my intention here is to somehow illustrate that lower IQ can be compensated by higher EQ for them to get on.
Non-fatal, attempted suicide could be the act of sending rescue calls
The suicide attempts with fewer fatality risks (e.g. non-lethal overdose, shallow wrists cuts etc) and obviously unplanned cases are thought to be driven largely by their emotions. The acts possibly are their unspoken means of expressing their troubled feeling or circumstances: their ultimate appeal to the empathetic nature of the others. In such cases, their action of self-harm is demonstrative with few intention to die. Such a mode of actions would only make sense to those with reasonable EQ, for what sought there is empathy by others. Following such incidents, what needed to them are appropriate cares and supports they need; without that the actions may repeat, possibly with increased fatality risks.
Another possible cause for acts of self-harm
Relatively rarely, a few may develop a mild dependency on endogenous opioid, beta-endorphin, which is released while the body undergoes physiologically stressful events. The affected might harm themselves using sharp objects to comfort themselves when non-lethal physical pain is perceived more bearable than affective distresses. Such individuals may better benefit from long-distance running or similarly stressful exercises that would also facilitate beta-endorphin release.
All unexpected events in life - IQ or EQ only represent partial functions in dealing with that
Life is unpredictable: small things can go unintended on daily basis, and the whole thing may take a wrong turn against what have been previously planned. Complications in human lives can be deadly forces, as no one can rarely live alone. We are susceptible to external controls which can emerge as biased rules in human societies, or as meteorological or environmental forces bringing natural disasters. Hardly anyone is exempt from all the probabilities of being struck by random events which could bring happiness or unhappiness. Within limits, however, certain incidents could possibly be avoided by having modest, sensible lifestyles, along with decent moral senses; abilities to self-discipline, being self-sufficient, trusting oneself, and general cautiousness are all important factors, independent of IQ or EQ, in avoiding bad situations which could trigger downward spirals.
References
Baron-Cohen S and Wheelwright S, 2004. The empathy quotient: an investigation of adults with Asperger syndrome or high functioning autism, and normal sex differences. J Autism Dev Disord. 34(2):163-75.
Batty GD et al., 2010. Psychosis alters association between IQ and future risk of attempted suicide: cohort study of 1 109 475 Swedish men, BMJ 340: c2506
II. A case of completed suicide
R.I.P. A. M. Turing, 1912 -1954.
When one is seriously considering to extinguish own existence, s/he would search a method which effectively terminate his/her life at once, carefully minimising chances of ending up in A&E with antidotes and equipments. Regarding critically ill with insufficient medical resources in developing countries, being treated at A&E for self-harm injuries should seem unthinkably wrong. To avoid the situation, the execution would be made at a right timing, well-planned in advance.
To give an example of the completed suicide, I would like to write about Alan M. Turing. Undoubtedly he was one of the brightest in a genuine sense. He was probably most well-known for his contributions on the theory of artificial intelligence. He was also one of the earliest to apply systematic analysis to describe biological phenomena in detail. The field of systems biology is still developing worldwide; some very fortunate ones are having exciting time playing with MATLAB® and plentiful of experimental data for parameters - I wish them good luck.
Turing was driven by foresighted purposes derived from his interdisciplinary interests and curiosities. His positive and productive attributes in life was clearly evident previously. At the end of Computing Machinery and Intelligence published in 1950 he wrote:
“ We can only see a short distance ahead, but we can see plenty there that needs to be done.”
Around that time he was keen on biological systems in neuronal cells and developmental cell growth. He worked forward and published The Chemical Basis of Morphogenesis in 1952 on his theory of pattern formation based on reaction-diffusion system, utilising parabolic second order partial differential equations, chemical equations, two-components reaction-diffusion equations.
Time was, however, harsh on him with respect to his personal life. He had a troublesome relationship that triggered a catastrophic situation, which placed him under unimaginable strains. Although he continued developing various ideas, he was suffering from lack of concentration and depression. He eventually turned to a Jungian psychological therapy involving dream analysis.
Turing died by ingesting cyanide and apple in June 1954, just before he turns the age of 42.
One could only imagine what theories and analysis he would have revealed to the world if all was going well for him at that time.
References
Turing, A. M. 1950. Computing Machinery and Intelligence, Mind 59: 433-460.
Turing A. M., 1952. The Chemical Basis of Morphogenesis, Phil Trans R Soc Lond B 237: 37-72.
Some information on Turing was taken from the writing by Hodges A, Turing, A Natural Philosopher, a part of the twelve essays in the series of The Great Philosophers, Raphael and Monk ed. 2000. (ISBN 0 75381 136 7)
This thread is written based on a string of thoughts on life and suicide, which was first initiated by encountering an epidemiological study published last year:
Psychosis alters association between IQ and future risk of attempted suicide: cohort study of 1 109 475 Swedish men
Batty GD, Whitley E, Deary IJ, Gale CR, Tynelius P, Rasmussen F, 2010. BMJ 340: c2506
The study concluded: Low IQ scores in early adulthood were associated with a subsequently increased risk of attempted suicide in men free from psychosis. A greater understanding of the mechanisms underlying these associations may provide opportunities and strategies for prevention.
I would like to expand the issue of attempted suicide beyond mere ineptness due to the lack of clear planning, though I should not totally exclude this possibility.
Low Intelligence Quotient scores may reflect their tendency to be driven emotionally
Individuals with low IQ scores are likely to under-perform academically and perhaps being short of a logic-based problem solving skill. Frustrated bullies at schools might belong to this category; one may find it hard to have an in-depth rational conversation with a bully, that is because their actions are often driven by emotions which inhibit coherent thinking process. The emotional inhibition of logical thinking might also contribute to their underperformance in IQ tests to some extent, for their negative emotions associated with being assessed in general; having lower self-esteem would be a contributing factor makes them susceptible to such effects.
Other possible measure in speculation
Even if individuals with low IQ scores do have deficits in the aspects of cognitive intelligence regardless of their emotional status, the majority (96% of the lowest IQ group in the study above) do not attempt suicide and may live quite happy life. One would speculate that there might be compensatory skills which make them suited to live in human society despite the deficit.
The idea of EQ (empathy quotient) has been introduced by Baron-Cohen as a measure of an ability to grasp others’ emotions and intentions by “social cues” given by facial expressions etc; EQ is a prerequisite for social skills, and low EQ is associated with higher functioning autism-spectrum condition with normal or above intelligence (Baron-Cohen and Wheelwright, 2004). The individuals with high EQ are regarded as being sympathetic in understanding the pains which others may feel; they likely are towards friends they love, but possibly less to enemies they disrespect or feel threatened by (evidently seen in human histories of wars and crimes). The individuals operate comfortably within a group are always quick to suss out the deviates of the group; low IQ with high EQ could altogether devalue and exclude high IQ with low EQ when the former failed to fully understand and acknowledge the latter and vice versa - it might appear slightly off-the-topic, but my intention here is to somehow illustrate that lower IQ can be compensated by higher EQ for them to get on.
Non-fatal, attempted suicide could be the act of sending rescue calls
The suicide attempts with fewer fatality risks (e.g. non-lethal overdose, shallow wrists cuts etc) and obviously unplanned cases are thought to be driven largely by their emotions. The acts possibly are their unspoken means of expressing their troubled feeling or circumstances: their ultimate appeal to the empathetic nature of the others. In such cases, their action of self-harm is demonstrative with few intention to die. Such a mode of actions would only make sense to those with reasonable EQ, for what sought there is empathy by others. Following such incidents, what needed to them are appropriate cares and supports they need; without that the actions may repeat, possibly with increased fatality risks.
Another possible cause for acts of self-harm
Relatively rarely, a few may develop a mild dependency on endogenous opioid, beta-endorphin, which is released while the body undergoes physiologically stressful events. The affected might harm themselves using sharp objects to comfort themselves when non-lethal physical pain is perceived more bearable than affective distresses. Such individuals may better benefit from long-distance running or similarly stressful exercises that would also facilitate beta-endorphin release.
All unexpected events in life - IQ or EQ only represent partial functions in dealing with that
Life is unpredictable: small things can go unintended on daily basis, and the whole thing may take a wrong turn against what have been previously planned. Complications in human lives can be deadly forces, as no one can rarely live alone. We are susceptible to external controls which can emerge as biased rules in human societies, or as meteorological or environmental forces bringing natural disasters. Hardly anyone is exempt from all the probabilities of being struck by random events which could bring happiness or unhappiness. Within limits, however, certain incidents could possibly be avoided by having modest, sensible lifestyles, along with decent moral senses; abilities to self-discipline, being self-sufficient, trusting oneself, and general cautiousness are all important factors, independent of IQ or EQ, in avoiding bad situations which could trigger downward spirals.
References
Baron-Cohen S and Wheelwright S, 2004. The empathy quotient: an investigation of adults with Asperger syndrome or high functioning autism, and normal sex differences. J Autism Dev Disord. 34(2):163-75.
Batty GD et al., 2010. Psychosis alters association between IQ and future risk of attempted suicide: cohort study of 1 109 475 Swedish men, BMJ 340: c2506
II. A case of completed suicide
R.I.P. A. M. Turing, 1912 -1954.
When one is seriously considering to extinguish own existence, s/he would search a method which effectively terminate his/her life at once, carefully minimising chances of ending up in A&E with antidotes and equipments. Regarding critically ill with insufficient medical resources in developing countries, being treated at A&E for self-harm injuries should seem unthinkably wrong. To avoid the situation, the execution would be made at a right timing, well-planned in advance.
To give an example of the completed suicide, I would like to write about Alan M. Turing. Undoubtedly he was one of the brightest in a genuine sense. He was probably most well-known for his contributions on the theory of artificial intelligence. He was also one of the earliest to apply systematic analysis to describe biological phenomena in detail. The field of systems biology is still developing worldwide; some very fortunate ones are having exciting time playing with MATLAB® and plentiful of experimental data for parameters - I wish them good luck.
Turing was driven by foresighted purposes derived from his interdisciplinary interests and curiosities. His positive and productive attributes in life was clearly evident previously. At the end of Computing Machinery and Intelligence published in 1950 he wrote:
“ We can only see a short distance ahead, but we can see plenty there that needs to be done.”
Around that time he was keen on biological systems in neuronal cells and developmental cell growth. He worked forward and published The Chemical Basis of Morphogenesis in 1952 on his theory of pattern formation based on reaction-diffusion system, utilising parabolic second order partial differential equations, chemical equations, two-components reaction-diffusion equations.
Time was, however, harsh on him with respect to his personal life. He had a troublesome relationship that triggered a catastrophic situation, which placed him under unimaginable strains. Although he continued developing various ideas, he was suffering from lack of concentration and depression. He eventually turned to a Jungian psychological therapy involving dream analysis.
Turing died by ingesting cyanide and apple in June 1954, just before he turns the age of 42.
One could only imagine what theories and analysis he would have revealed to the world if all was going well for him at that time.
References
Turing, A. M. 1950. Computing Machinery and Intelligence, Mind 59: 433-460.
Turing A. M., 1952. The Chemical Basis of Morphogenesis, Phil Trans R Soc Lond B 237: 37-72.
Some information on Turing was taken from the writing by Hodges A, Turing, A Natural Philosopher, a part of the twelve essays in the series of The Great Philosophers, Raphael and Monk ed. 2000. (ISBN 0 75381 136 7)
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