Non-monotonic effects of GABAergic synaptic inputs on neuronal firing.

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2022-06-06

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Abstract

GABA is generally known as the principal inhibitory neurotransmitter in the nervous system, usually acting by hyperpolarizing membrane potential. However, GABAergic currents sometimes exhibit non-inhibitory effects, depending on the brain region, developmental stage or pathological condition. Here, we investigate the diverse effects of GABA on the firing rate of several single neuron models, using both analytical calculations and numerical simulations. We find that GABAergic synaptic conductance and output firing rate exhibit three qualitatively different regimes as a function of GABA reversal potential, EGABA: monotonically decreasing for sufficiently low EGABA (inhibitory), monotonically increasing for EGABA above firing threshold (excitatory); and a non-monotonic region for intermediate values of EGABA. In the non-monotonic regime, small GABA conductances have an excitatory effect while large GABA conductances show an inhibitory effect. We provide a phase diagram of different GABAergic effects as a function of GABA reversal potential and glutamate conductance. We find that noisy inputs increase the range of EGABA for which the non-monotonic effect can be observed. We also construct a micro-circuit model of striatum to explain observed effects of GABAergic fast spiking interneurons on spiny projection neurons, including non-monotonicity, as well as the heterogeneity of the effects. Our work provides a mechanistic explanation of paradoxical effects of GABAergic synaptic inputs, with implications for understanding the effects of GABA in neural computation and development.

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10.1371/journal.pcbi.1010226

Publication Info

Abed Zadeh, Aghil, Brandon D Turner, Nicole Calakos and Nicolas Brunel (2022). Non-monotonic effects of GABAergic synaptic inputs on neuronal firing. PLoS computational biology, 18(6). p. e1010226. 10.1371/journal.pcbi.1010226 Retrieved from https://hdl.handle.net/10161/25453.

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Scholars@Duke

Calakos

Nicole Calakos

Lincoln Financial Group Distinguished Professor of Neurobiology
Brunel

Nicolas Brunel

Duke School of Medicine Distinguished Professor in Neuroscience

We use theoretical models of brain systems to investigate how they process and learn information from their inputs. Our current work focuses on the mechanisms of learning and memory, from the synapse to the network level, in collaboration with various experimental groups. Using methods from
statistical physics, we have shown recently that the synaptic
connectivity of a network that maximizes storage capacity reproduces
two key experimentally observed features: low connection probability
and strong overrepresentation of bidirectionnally connected pairs of
neurons. We have also inferred `synaptic plasticity rules' (a
mathematical description of how synaptic strength depends on the
activity of pre and post-synaptic neurons) from data, and shown that
networks endowed with a plasticity rule inferred from data have a
storage capacity that is close to the optimal bound.



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