Alcohol addiction

Written by Quek Ten Cheer

Edited by Sasinthiran


Alcohol addiction is a serious societal issue that can lead to many domestic and social problems. One way to prevent this issue from becoming worse is to understand more about how alcohol, as a drug, causes these problems. In this article, we aim to inform readers on the biological effects of alcohol, especially on the brain, and how addiction is currently being treated medically.

Alcohol and crime

Alcohol has been implicated in between 57% and 85% of violent crimes1. In addition, many suicides are committed under the influence of alcohol2. The most likely mode of action for alcohol in stimulating aggression is its general disinhibiting effects on behaviour. Alcohol silences higher cortical areas responsible for impulse control, often leading to behaviour that is normally actively suppressed, including aggression.

What is alcohol?

Alcohol is a psychotropic drug, which means that it is a drug that affects our mental state. This places alcohol (commonly referred to as ethanol in scientific literature) in the same category as:

  • Cannabinoids (the active material in cannabis, or marijuana);
  • Nicotine (one of the active psychotropic agents in cigarettes and cigars);
  • Psychostimulants, much stronger drugs which include cocaine, MDMA (commonly known as ecstasy), and methamphetamine (you might know it as the blue ‘meth’ from Breaking Bad);
  • Opiates, morphine-like drugs such as heroin (diacetyl morphine).3,4

In addition, alcohol is a biphasic drug5; small amounts act as a stimulant by reducing inhibition and producing mild euphoria. Higher doses depress the central nervous system (CNS) that will initially promote relaxation but lead to the person experiencing effects such as ataxia (uncoordinated movement), sedation and general ‘drunkenness’.

Fun fact: Asian Flush

Some of us get the ‘Asian flush’, i.e. our faces become reddish from drinking (because the body is unable to quickly metabolize acetaldehyde, a by-product of alcohol metabolism). (Acetaldehyde is the main culprit behind headaches, nausea, and hangovers).

In fact, the reaction that breaks down acetaldehyde, by means of the enzyme aldehyde dehydrogenase, is faster in alcoholics than in non-alcoholics.6


Alcohol addiction

What makes a person addicted to alcohol? The 5th edition of the Diagnostic and Diagnostic and Statistical Manual of Mental Disorders (DSM-V), recognises excessive use of alcohol as a disorder in which patients are diagnosed with the substance use disorder when they display at least 2 of the following 11 symptoms within a 12 month period:

  • Consuming more substance than originally intended
  • Worrying about stopping or consistently failed efforts to control one’s use
  • Spending a large amount of time using the substance, or doing whatever is needed to obtain them
  • Use of the substance results in failure to “fulfil major role obligations”
  • “Craving” the substance
  • Continuing the use of a substance despite health problems caused or worsened by it
  • Continuing the use of a substance despite its having negative effects in relationships with others
  • Repeated use of a substance in a dangerous situation (e.g. when driving a car)
  • Giving up or reducing activities in a person’s life because of the substance use
  • Building up a tolerance to the alcohol or drug. Tolerance is defined by the DSM-V as “either needing to use noticeably larger amounts over time to get the desired effect or noticing less of an effect over time after repeated use of the same amount.”
  • Experiencing withdrawal symptoms after stopping use. Withdrawal symptoms typically include, according to the DSM-V: “anxiety, irritability, fatigue, nausea/vomiting, hand tremor or seizure in the case of alcohol.”

As can be seen from the DSM-V definition of alcohol use disorder, the interpretation of an individual’s use of alcohol as being excessive and leading to dysfunction is subjective and must be considered together with environmental and contextual factors.

However, alcohol addiction is also largely a problem that needs to be treated by addressing the environmental factors in addition to its targeted pharmacological treatment; prescribed medicines alone cannot fully treat the condition.

There is a plethora of literature on many illicit drugs of abuse, in particular cocaine. They demonstrate the pharmacological basis by which people become addicted to these drugs, in hopes of deriving better pharmacological treatment which targets, mainly, the addiction pathways in the brain.

Let’s talk about the brain

Firstly, if we want to know anything about alcohol addiction, we need to start with the very-important mesolimbic pathway, commonly called the ‘reward pathway’ for its role in addiction and associated disorders. You can recall this term and its position in the brain by the fact that ‘meso’ means ‘middle’ in Greek, and it is located in the middle of the brain. Thus ‘mesolimbic’ also means the midbrain, or ‘middle brain’.


The mesolimbic pathway, highlighted in the opaque blue in the above figure7, connects the ventral tegmental area (VTA) to the nucleus accumbens (NAC). It is also referred to as a dopaminergic pathway (abbreviated DAergic pathway) because it transmits the neurotransmitter dopamine throughout the two areas.8 Don’t underestimate its small size! It is the most significant neural pathway in the brain within which changes occur in all known forms of addiction. It is widely studied in the reward circuitry underlying drug abuse, depression, addiction, as well as conditioning and studies on human behaviour.

The brain is addicted to pleasure and positive effects; more specifically, it craves any activity which leads to the activation of dopaminergic pathways that trigger the brain’s reward response with the release of the neurotransmitter dopamine 9. Research shows that addictive substances such as alcohol are in fact addictive primarily because they activate such pathways leading to a reward response, leaving the brain craving for more 10. In other words, the more a particular behaviour, such as taking alcohol, triggers the reward centers of the brain, the more the brain seeks out such behaviour through learned operant conditioning by positive reinforcement. This then increases the occurrence of that behaviour in the future (thus, addiction).


A 2003 study done by Boileau et al.  have found that the consumption of alcohol stimulates the release of dopamine in the nucleus accumbens12. Dopamine (commonly abbreviated as DA in literature) was synthesised over 100 years ago (in 1910), but was recognised to be a neurotransmitter many decades later, in the 1950s. In the brain, dopamine is produced in hypothalamic neurons as well as neurons of the VTA and substantia nigra.13


After secretion of DA into the synapse, the intact molecule is reabsorbed into the neurons by a specific transporter, the dopamine transporter (DAT). They are then metabolised within cells by monoamine oxidase (MAO) or catecholamine O-methyl transferase (COMT); both enzymes convert dopamine into inactive products.

Compounds that inhibit DAT, such as cocaine (meaning the effect of dopamine is prolonged in the synapse as its concentration remains elevated), cause mood elevation and addiction.

Compounds that inhibit MAO (meaning DA does not get broken down after being re-uptaken) are effective antidepressants, which includes selective serotonin reuptake inhibitors (SSRIs), such as Prozac (you might know it as ‘fluoxetine’ or ‘fluoxetine HCl’ if you’ve ever had hypochondriac tendencies).

Neurotransmitters/neuropeptides that influence alcohol consumption

In alcohol addiction, there are several neurotransmitters and neuropeptides in the brain that influence alcohol consumption. These include Glutamate, GABA (gamma-aminobutyric acid), nACHR/glycine, DA/5-HT, Cannabinoids, Opioids, and CRF/NPY.11


Potassium channels and GABAA receptors in the VTA

Among the potential means by which alcohol might influence the firing rate of dopaminergic neurons in the brain, the best studied are the actions of ethanol on potassium channels and GABAA receptors in the VTA.

Alcohol functions as an agonist of GABAA receptors and its binding to these receptors leads to the inhibition of the post-synaptic neurons. Alcohol, by binding to GABAA receptors on VTA GABAergic interneurons, may disinhibit (activate) VTA dopaminergic neurons that project to the NAc (nucleus accumbens) which is involved in producing a feeling of pleasure and mood elevation (Nestler, 2005)14.

Interestingly, autopsies of alcoholics’ brains have revealed that they were in a hypodopaminergic state, which explains why alcoholics would continue to seek out more alcohol to achieve the sensation of pleasure and mood elevation they have learnt to associate with alcohol consumption.


Pharmacology of alcohol on the brain

Alcohol is generally viewed as being an unspecific pharmacological agent, but based on recent studies it has been shown to act by disrupting distinct receptor or effector proteins via direct or indirect interactions. There is a widespread plethora of literature on the abuse of psychostimulants, especially cocaine. (There is, however, scarce publications on abuse of alcohol.)

At concentrations in the 5-20mM range, which is the legal intoxication range for driving in many countries, alcohol directly interferes with the functions of several ion channels and receptors.11

Recent molecular pharmacology studies demonstrate that alcohol has a few primary targets, which include NMDA, GABAA, 5-HT3, nAChR, as well as L-type Ca2+ channels and GIRK, where concentrations as low as 1mM produce alterations in the functions of these receptors and ion channels. Some of these are outlined below:

NMDA receptors

NMDA receptors are commonly associated with excitatory glutamatergic activity and in the formation of Long Term Potentiation (LTP) which is essential for memory formation. Disruption of this receptor function by alcohol explains why many would find it difficult to remember the events of a night out when heavily intoxicated15– also known as ‘blackout’.

More inhibitory GABAA receptor activity

Moreover, alcohol has been found to stimulate inhibitory GABAA receptor activity by serving as an agonist in the hippocampus, an area of the brain associated with memory formation, contributing to this brief amnesic episode16.

Alcoholic activation of inhibitory GABAA activity of neurons projecting to higher areas of the cortex brings about reduced inhibitions and anxieties and facilitates better social interactions while reducing impulse control.

In fact, recovering alcohol addicts often experience life-threatening seizure episodes as a withdrawal symptom due to a rebound effect whereby inhibitory GABAA receptors become hypoactive in the absence of alcohol.


Alcohol also functions as an endorphin, mimicking the effects of opiate drugs and producing an endorphin ‘high’ associated with the use of such drugs.

More inhibitory neuromodulator activity

Alcohol has also been found to increase the activity of inhibitory neuromodulators such as adenosine which leads to sedative effects and a reduced state of awareness.

Treatment of alcohol addiction

It is estimated that 7.9% of people 12 years or older in the U.S. require help for alcoholism, more than twice the percentage of the population estimated to require treatment for the abuse of all illicit drugs collectively.

Alcohol use has been linked to diseases and ailments such as malnutrition (due to the ‘empty calories’ of alcohol) and in particular fetal alcohol syndrome (which causes developmental and physical abnormalities in the offspring of mothers who consume alcohol during pregnancy).

Alcohol abuse has been linked to domestic abuse, sexual assault, and can destroy families.

Treatment of alcohol addiction is largely based on psychological and psychiatric help, as compared to pharmacologically-based treatment.

Alcohol addiction requires a multi-pronged approach to treatment. Drugs alone show little effect insofar as treatment is concerned; environmental factors need to be addressed when treating alcohol addiction. Treatment involves the facilitation of abstinence and the prevention of relapse.

Pharmacologic treatment is often used to reduce withdrawal symptoms, but thus far has not been effective in preventing relapse. It is a theoretical possibility, however, that medications which block the reinforcing effects of drugs or drug-induced plasticity might reduce drug craving and the likelihood of relapse. Such medications can be effective if they can act without interfering with the body’s responsiveness to natural rewards (e.g. anhedonia, when the abuser suddenly finds a drastic disinterest in normal daily activities). Currently, no reward-reducing drug treatment has yet been established for clinical use.


  1. Cacioppo J., Freberg L., 2013. Discovering Psychology: The Science of Mind, Briefer Version. Wadsworth, Cengage Learning, Chapter 11, pp. 600.
  2. Sher L. (2006). Alcohol Consumption and Suicide. QJM, 99(1):57-61.
  3. Nestler, E. J.; Hyman S. E.; Malenka R. C. Molecular Neuropharmacology: A foundation for clinical neuroscience (2nd) McGraw-Hill. pp. 364-388
  4. Pierce, C.R., Kumaresan V., 2006. The mesolimbic dopamine system: The final common pathway for the reinforcing effect of drugs of abuse? Neuroscience and behavioural reviews, 30, Issue 2, pp. 215-238.
  5. Glossary: Drugs and Alcohol. (n.d.). Retrieved July 16, 2016, from
  6. Campbell, M. K., Farrell, S. O. (2009,2012). Biochemistry. Brooks/Cole Cengage Learning. pp. 689.
  7. Mesolimbic pathway. (2015) [Image from]
  8. “Mesocorticolimbic Dopaminergic Neurons.” Neuropsychopharmacology: The Fifth Generation of Progress. Retrieved from
  9. Insel, T. R., 2003. Is Social Attachment an Addictive Disorder?. Physiology and Behavior, 79(3), pp. 351-357.
  10. Koob, G. F. & Moal, M. L., 1997. Drug Abuse: Hedonic Homeostatic Dysregulation. Science, Volume 278, pp. 52-58
  11. Vengeliene V.; Bilbao A.; Molander A.; Spanagel R. Neuropharmacology of alcohol addiction. British Journal of Pharmacology (2008) 154, 299-315.
  12. Boileau I. et. al, Alcohol promotes dopamine release in the human nucleus accumbens. Synapse 49:226-231 (2003). Retrieved from
  13. W. Pfaff (ed.), Neuroscience in the 21st Century, DOI 10.1007/978-1-4614-1997-6_51, # Springer Science+Business Media, LLC 2013
  14. Nestler, E. J. Is there a common molecular pathway for addiction? Nature Neuroscience 8, 1445 – 1449, 2005
  15. Lovinger, D. M.; White, G.; Weight, F. F. NMDA receptor-mediated synaptic excitation selectively inhibited by ethanol in hippocampal slice from adult rat. Journal of Neuroscience 10:1372. 1379, 1990.
  16. Weiner, J. L.; Zhang, L.; Carlen, P. L. Potentiation of GABAA-mediated synaptic current by ethanol in hippocampal CA1 neurons: Possible role of protein kinase C. Journal of Pharmacology and Experimental Therapeutics 268:1388. 1395, 1994

Seminar on Cellular Neuroscience

Written by Sasinthiran

Edited by Xin Chen, Yingchen and Keshiniy

Image: Overhead view of a voltage-dependent potassium ion channel shows four red-tipped “paddles” that open and close in response to positive and negative charges. (

On the 12th of February, members of NUS Neuroscience Student Interest group convened for a seminar on Cellular Neuroscience, as part of the fortnightly seminar series hosted by group members to explore different topics in neuroscience. The seminar was hosted by Enos Goo (Year 3, Life Sciences).

The seminar started off with a presentation on the basic principles of electrophysiology and the electrochemical basis of the membrane potential that is key for the generation of Action Potentials in neurons. Enos then touched on the remarkable diversity of individual neurons in terms of the vast variations in ion channels that confer unique properties when expressed in neurons. Differential expression and distribution of such ion channels allow for unique modulation of the membrane potentials of neurons and thus contribute to their diversity.

Next, Enos shared about specific types of ion currents such as the dendritic A-type current, and the dendritic H current which confer different electrophysiological properties to neurons through the action of specific ion channels. For example, it was noted that thalamic spindles observed during sleep are a result of an interaction between a calcium ion current and an inward pacemaker dendritic H current in neuronal populations at the thalamus. This property allows for the generation of rhythmic bursts of action potentials  that allows for a reduction in relaying of sensory input from sense organs to higher cortical areas for processing, since the thalamus functions as a relay centre for relaying such information (save for that of olfactory input).

It was noted that while science takes a reductionist approach in understanding the mechanisms of action in biological systems, a more global perspective yields greater insight into the more complex emergent properties of the components of such a biological system working together. An analogy was drawn to to our human society which is composed of numerous unique individuals, with not one of us being indispensable to the functioning of society as a whole. Thus, studying how a population of diverse neurons work together in neural circuits to give rise to complex emergent properties such as consciousness, the notion of morality etc., warrants significant interest.

It was also shared that back-propagated action potentials can be recorded in dendrites (albeit with a slight delay) as they too possess voltage-gated channels to support the propagation of action potentials.

The second part of the seminar involved discussing the notion of Intrinsic plasticity which involves the dynamic modulation of the electrophysiological properties of a neuron which affects their excitability and the computation of spatial and temporal summation of input the neuron receives ( as opposed to synaptic plasticity which is implicated in learning and memory) and its implications in disorders of the central nervous system. It was noted that in aging, an enhanced after-hyperpolarisation is seen at the end of action potentials and that this has been attributed to aberrant functioning of potassium ion channels which usually return the neuron to its resting membrane potential at the end of an action potential. The aberrant functioning of such channels with age could be due to the accumulation of mutations throughout life.

In epilepsy, it was noted that there was an aberrant down-regulation of potassium ion current and an enhanced persistent sodium ion current, leading to an increased intrinsic excitability of the neurons and hence the rapid burst of action potentials characteristic of an epileptic episode. In neurodegenerative diseases such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD), changes in the electrophysiological properties of the neurons have been observed prior to neuronal death (e.g. changes in ion channel expression and distribution). Moreover, degeneration of the Septal nuclei in AD leads to reduced cholinergic input to the hippocampus. This leads to an increased M current (efflux of potassium ions) and an enhanced after-hyperpolarisation of hippocampal neurons following action potentials, thus leading to the suppression of the neurons which usually fire in rapid bursts. It is noteworthy that firing in rapid bursts is an essential trait for memory coding and consolidation.

The seminar concluded with an interactive discussion on a few key topics. First, we reviewed the role of astrocytes in the ‘tripartite synapse’ and acknowledged the paradigm shift in considering the role of glial cells in the nervous system from one that views them as passively contributing to the matrix that hold neurons together in the brain to the view that they have active modulatory effects on neuronal activity (e.g. tripartite synapse’).

Next, we discussed the use of optogenetics (transfection of genes coding for light-sensitive rhodopsin activated ion channels into neurons) and considered potential applications of this technology in treating depression for example by activating serotonergic neurons instead of relying on drugs that have side-effects. However, the limitation of the technology is that light has to be directed towards the population of neurons via an optic cable (invasive). We also briefly discussed the possible physiological mechanism through which populations of neurons in migratory birds an other animals can use the earth’s magnetic field patterns to guide their migrations. We considered the possibility of using AC magnetic fields to heat (via eddy currents) a nanoparticle fused to an ion channel as a means of controlling the closure of the inactivation gate. This allows for a non-invasive way to control the activation of specific neuronal populations (a greater degree of spatial resolution).

Finally, we discussed the fact that a single nucleotide substitution on the voltage-gated sodium ion channel gene in pufferfishes allow them to be resistant to their own toxin (tetrodotoxin) which paralyses the nervous system of those who come into contact with it by inactivating the voltage-gated sodium ion channels. thus no action potential can be generated as the membrane cannot be depolarised by an influx of sodium ions. It is notable that this discovery was made by a research team based at NUS, headed by Professor Soong Tuck Wah.

The slides used for the presentation during the seminar can be found here (courtesy of Enos Goo): Cellular Neuroscience presentaion slides [943273]

Seminar on Neurons, Glia and Neurophysiology

Written by Sasinthiran

Edited by Xin Chen, Yingchen and Keshiniy


On the 29th of January 2016, the NUS Neuroscience Student Interest Group conducted its first seminar titled ‘Neurons, Glia and Neurophysiology’, hosted by Sasinthiran (Year 3, Life Sciences).

Participants were provided reading material on the topic compiled from various sources two weeks prior to the seminar. At the start of the seminar, participants attempted to complete a quiz (18 questions) in groups of 3-4 members within 30 minutes.

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The quiz questions were then discussed in an interactive format whereby groups had to defend and justify their answers if they differed from that of other groups.

The discussion started off with a question on the permeability of the blood-brain barrier (BBB). It was first highlighted that the components of the BBB are the tight junctions between the capillary endothelial cells, the basal lamina of the capillary and the perivascular foot processes of astrocytes (a type of glial support cell). It was noted that water and water soluble agents were able to diffuse across via the tight junctions while charged species such as sodium ions were first transported by trans-membrane protein pumps/ channels into the endothelial cells of the blood capillaries and subsequently into the brain. Lipid soluble molecules are free to diffuse through the phospholipid bi-layer of the endothelial cell membranes while larger charged molecules such as glucose ( primary energy source of the brain) and amino acids are transported by by trans-membrane transport proteins. Other solutes may also be transported by receptor-mediated endocytosis when they bind to their specific receptors on the surface of the endothelial membrane, as well as adsorptive transcytosis. It was noted that due to tight junctions between the capillary endothelial cells, leukocytes a(white blood cells) and other immune cells may not be able to cross the BBB to a great extent and hence the brain relies on a local population of cells known as the microglia (not derived from neuroectodermal lineage but from immune cell lineage) which mediate local immune function (e.g. phagocytosis and secretion of inflammatory factors such as interleukins to attract other immune cells).

Next, the discussion focused on the profile of an action potential (AP). It was noted that the refractory period (decrease in membrane potential to a value more negative than the resting membrane potential) after the peak in voltage of an AP had two parts: the absolute refractory period (lasting 1 msec due to the closing of the inactivation gate of sodium ion channels) during which no  action potential can be generated followed by the relative refractory period during which a higher than usual stimulus is required to depolarize the membrane to threshold potential in order to trigger an action potential. It was also noted that the fall in membrane potential below that of resting potential because the voltage-gated potassium channels that opened at the peak of the AP were slow to close and hence allowed more potassium ions to diffuse out of the neuron, down its concentration gradient.

The discussion then looked at the factors affecting the speed of conduction along an axon and 4 factors were identified: higher temperature, wider diameter of the axon, increased myelination (insulation) and decreased length (between nodes of ranvier) all favor faster conduction. It was also noted that different classes of axons with different diameter and myelination properties exist in the body to serve their particular functions. for example, when someone hits his toes against a hard surface, the faster A-delta fibres that are myelinated conduct a sharp pain sensation while the slower unmyelinated C fibres conduct the slow, dull pain that follows.

Next, we reviewed the various gating mechanisms of ion channels: ligand-gated, mechanosensitive (e.g. stretch-activated), voltage-gated, photon-gated (responds to light) or even ungated. We briefly discussed the recent development of optogenetics in which genes coding for a light-sensitive receptor has been transferred and expressed in select populations of mice neurons to modulate their behavior when that region is exposed to light via an optic fiber cable.

Our discussion then moved on to define the terms that describe a cell membrane’s potential. Depolarisation represents a rise in membrane potential from a negative resting potential towards the potential of 0mV (same internal potential as outside of the cell). Repolarisation represents a drop in membrane potential from 0mV to a more negative potential. Hyperpolarisation refers to a drop in membrane potential to a value more negative than that of the resting potential.

Next, we had a brief review of the activity at the neuromusccular junction (NMJ) that results in the contraction of skeletal muscle fibres for movement. It was noted taht acetylcholine was the primary neurotransmitter released at the NMJ.

The discussion then moved on to briefly touch on the fact that groups of axonal tracts that run up and down the spinal cord are arranged in columns. It was noted that such tracts are called projections when observed in the brain.

We then proceeded to discuss the factors responsible for the establishment and maintenance of the action potential: the unequal distribution of ions inside and outside the neurons (sodium, chloride and calcium ions are concentrated outside the cell while the inside of the cell has a higher concentration of potassium ions and other large non-difussible anions that also contribute to the negative resting membrane potential), the action of the sodium-potassium ATPase pump which pumps out 3 sodium ions and pumps in 2 potassium ions against their concentration gradient (thereby resulting in the net loss of one positive ion) as well as the free diffusion (leakage) of potassium ions out of the cell through leaky potassium channels.

Next, the discussion focused on the role of glia in the nervous system. It was noted that there has been a paradigm shift from considering glia simply as cells that form the matrix that hold the neuron together to one that accepts their active role in the nervous system. For example, astrocytes have been found to form a ‘tripartite synapse’ with post- and pre-synaptic neurons and even modulate and synchronize their communication through the release of gliotransmitters (visualised trhough the observation of signature calcium waves in the astrocytes which lead to the fusion of vesicles containing gliotransmitters to the astrocyte membrane to release the gliotransmitters). Microglia have the potential to differentiate into astrocytes or neurons, modulate local immune response through phagocytosis and release of cytokines such as interleukins to attract other immune cells (inflammation) as well as guide young neurons during neuronal migration in early development. Schwann cells (in the PNS) and oligodendrocytes (in the CNS) form myelin sheaths around axons to nourish the cells and at the same time speed up the conduction of action potentials. It was noted that the key difference between neurons and glia is that glia do not generate action potentials. It was noted, however, that a population of the pacemaker cells in the sinoatrial (SA) and atrioventricular (AV) nodes of the heart are the only other cells outside of the nervous system that are capable of generating their own action potentials.

The next question revisited the profile of the action potential and it was noted that the rapid depolarisation of the membrane was due to the rapid influx of sodium ions through their voltage-gated channels (more open upon membrane potential reaching threshold potential), driven by both their electrical and chemical gradients into the neuron.

Next, we looked at the summation of input from pre-synaptic neurons in a post-synaptic neuron that could either lead to to an EPSP (excitatory post-synaptic potential) or an IPSP (inhibitory post-synaptic potential). It was noted that if the excitatory effect is greater than the inhibitory effect but less than the threshold of stimulation, the result is a subthreshold EPSP. Furtehrmore, if the excitatory effect is greater than the inhibitory effect and reaches or surpasses the threshold level of stimulation, the result is a threshold or suprathreshold EPSP and one or more nerve impulses. Alternatively, if the inhibitory effect is greater than the excitatory effect, the membrane hyperpolarizes, resulting in inhibition of the postsynaptic neuron and the inability of the neuron to generate a nerve impulse.

Subsequently, we went on to review the fact that stimuli intensity is encoded in the frequency of action potentials which are of equal magnitude (amplitude). The higher the stimuli intensity, the higher the frequency of the action potential.

We also identified that the falling of the membrane potential towards resting membrane potential was due to the opening of voltage-gated potassium channels at the peak of the action potential, leading to an efflux of potassium ions out of the cell, down its concentration gradient. As noted before, the slow closure of these channels results in the drop in membrane potential past that of the resting membrane potential (refractory period).

Next, we briefly discussed the experiment conducted by German physiologist Otto Loewi which proved that neurons communicated through chemical messengers that we now know to be neurotransmitters. He stimulated one frog’s heart, collected fluid around it, transferred it to another frog’s heart, and saw change in its heart rate.

We then moved on to briefly discuss a thought experiment and concluded that if we wanted to cause the pre-synaptic terminal of an axon to release its neurotransmitter without an action potential, we could inject calcium into its pre-synaptic terminal. This is because of the fact that the influx of calcium into the pre-synaptic terminal (usually when an action potential reaches the pre-synaptic terminal and depolarise the membrane, causing the opening of voltage-gated calcium ion channels) results in teh fusion of synaptic vesicles containing neurotransmitters to the pre-synaptic membrane.

Next, we discussed the differences between metabotropic and ionotropic receptors. Ionotropic receptors have a pore which opens/ closes to directly control the passage of ions while metabotropic receptors when activated, trigger an intra-cellular signalling cascade to cause an ion channel to open/ close in response (indirect control of movement of ions). Thus ionotropic receptors have fast acting effects and and its action is short-lived while metabotropic receptors have slower effects that last longer (due to signal amplification in the signalling cascade).

The seminar concluded with the discussion of the learned concepts in more challenging application questions. Firstly, we discussed the scenario whereby an action potentaial is triggered at same time from both directions of an axon (in both the orthodromic and antidromic directions). In this case, we concluded that when both action potentials meet at a point along the axon, they will not propagate any further. This is because the region just behind the each action potential is undergoing a 1 msec absolute refractory period in which no action potential can be generated since the voltage -gated sodium ion channels have their inactivation gates closed for that period.. Thus both the orthodromic and antidormic action potentials cannot proceed ahead in their direction of propagation.

There was also a short sharing on the role of GABA as an excitatory neurotransmitter in the neurons of fetuses (due to the high intracellular chloride ion concentration). The role of Glutamate as both an excitatory and inhibitory neurotransmitter in the retina was also discussed and it was noted that the effect of neurotransmitters is dependent on the type of receptor it binds to (metabotropic or ionotropic).

The quiz questions, answers and further information on the topics discussed can be found here: Neurons Glia and Neurophysiology.