Brain Modeling Using NEURON, Interneurons, and Resonant Circuits

Research has shown that a higher rate of spiking activity in cerebral cortical Fast Spiking interneurons enhance gamma band (20-80 Hz) oscillations. In contrast, higher rates of spiking activity in Regular Spiking neurons enhance alpha band (around 8 Hz) oscillations. Optogenetic techniques made it possible to carry out these experiments by targeting a specific cell type with genetic manipulations that result in expression of light activated channels. When these channels are activated they cause the neurons to fire action potentials.

The neural circuit underlying Fast Spike interneuron enhanced gamma band oscillations has been relatively well defined. The Fast Spiking inhibitory interneurons release GABA onto GABA-A receptors on Regular Spiking pyramidal neurons. The time constant of GABA-A synaptic inhibition is a key factor controlling gamma rhythmicity. The mechanisms driving alpha band oscillations through Regular Spiking neuron activity are less clear. The authors of the recent paper “Computational modeling of distinct neocortical oscillations driven by cell-type selective optogenetic drive: separable resonant circuits controlled by low-threshold spiking and fast-spiking interneurons” (published November 22, 2010 in Frontiers in Human Neuroscience) studied an existing computational model of the cerebral cortex used to explain Fast Spiking interneuron driven gamma band oscillations to see if it was sufficient to account for Regular Spiking neuron driven alpha band oscillations.

The research team used and extended existing computational models of the cerebral cortex that ran in the NEURON simulation environment. I was very excited to see stated in the paper’s methods that “Upon publication, the model will be made available in the model DB database.” ModeDB is the computation neuroscience model repository within the larger SenseLab online data repository.

Note: Tomorrow we will take a close look at NEURON and the computational neuroscience models associated with this paper made available in ModeDB.

The research team found that, while gamma band enhancement due to driving activity in Fast Spiking interneurons was replicable in a “canonical” Fast Spiking interneuron–Regular Spiking neuron network, lower frequency (alpha band) enhancement due to driving activity in Regular Spiking neurons was not. To reproduce the enhancement of alpha band oscillation due to driving activity in Regular Spiking neurons required the addition of a Low Threshold Spiking inhibitory interneuron population that generated extended inhibition.

The results of this theoretical work strongly suggest four features essential to the contrasting predominant cerebral cortical oscillations due to driving Fast Spiking interneurons or Regular Spiking neurons:

• evoking spikes in the Low Threshold Spiking interneurons depended on highly synchronous excitatory input
• inhibitory connections from Fast Spiking interneurons to Low Threshold Spiking interneurons
• the duration of Low Threshold Spiking interneuron to Regular Spiking neuron induced inhibition
• the distal dendrites of Regular Spiking neurons received synaptic noise that generated noise dependent spikes

This is an excellent computational neuroscience paper that took a look at a range of possible neural circuits and mechanism to account for experimentally observed phenomena and provided plausible answers with specific predictions that can be experimentally tested.