Tuesday, January 22, 2013

How to Build a Neuron: Step 5

And now, the final step in how to build your computational model of a neuron: Add Synaptic Channels. All the steps in this series can be found here.
Synapses connect neurons (source)
So you already have a neuron, and you've added intrinsic channels to it. The next thing you want to do is add synaptic channels so you can hook this neuron up to other cells.

The main synaptic channels you want to add are the excitatory channels: NMDA and AMPA and the inhibitory channel GABA. These channels don't have the same kind of activation and inactivation curves and the intrinsic channels do because they aren't activated by voltage, they are activated by a neurotransmitter.

AMPA and NMDA receptors are activated primarily by glutamate, and cause an influx of sodium and calcium ions. Since both sodium and calcium ions are positively charged, this depolarizes the cell membrane and brings it closer to firing an action potential.

AMPA receptors (source)
GABA receptors, on the other hand are primarily activated by GABA, and cause and influx of chloride ions into the cell. Because chloride ions are negatively charged, this hyperpolarizes the cell membrane and brings it further away from firing an action potential.

So if you want to have a realistic model of a neuron, you need to add an approximation of these channels. This is easier than adding intrinsic channels, because it is an on/off style (binary) rather than an analogue activation. So basically you just put in the parameters you want like how fast does the channel open and close, how much current does it allow through when activated, and where are they on the neuron.

Of course deciding these parameters is not always easy. A paper out this year in PLoS Computational Biology describes 4 different ways the NMDA receptor can be configured and analyzes the consequences during different stimulation patterns. 

Evans et al., (2012) Figure 3
The 4 NMDA configurations (based on the 4 different GluN2 subunits) vary in their sensitivity to a magnesium block, how fast they decay, and their maximal current. Above are their responses to the same stimulation patterns (an STDP protocol). Even though they were all receiving the same input pattern, they each show a very different response.

So when considering adding synaptic channels to your model neuron, take the time to find out what the configuration of the receptors should actually be in the type of neuron you are building.

© TheCellularScale

If you are good at following clues, you will realize that I am very, very familiar with this paper.

ResearchBlogging.orgEvans RC, Morera-Herreras T, Cui Y, Du K, Sheehan T, Kotaleski JH, Venance L, & Blackwell KT (2012). The effects of NMDA subunit composition on calcium influx and spike timing-dependent plasticity in striatal medium spiny neurons. PLoS computational biology, 8 (4) PMID: 22536151

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