Written by Sasinthiran

Edited by Xin Chen, Yingchen and Keshiniy

potassium_channels-264px.gif
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. (https://www.bnl.gov/bnlweb/history/nobel/nobel_03.asp)

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]

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