Keijser, Joram; Sprekeler, Henning; (2022) Optimizing interneuron circuits for compartment-specific feedback inhibition. PLOS Computational Biology , 18 (4) , Article e1009933. 10.1371/journal.pcbi.1009933.

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Abstract

Cortical circuits process information by rich recurrent interactions between excitatory neurons and inhibitory interneurons. One of the prime functions of interneurons is to stabilize the circuit by feedback inhibition, but the level of specificity on which inhibitory feedback operates is not fully resolved. We hypothesized that inhibitory circuits could enable separate feedback control loops for different synaptic input streams, by means of specific feedback inhibition to different neuronal compartments. To investigate this hypothesis, we adopted an optimization approach. Leveraging recent advances in training spiking network models, we optimized the connectivity and short-term plasticity of interneuron circuits for compartment-specific feedback inhibition onto pyramidal neurons. Over the course of the optimization, the interneurons diversified into two classes that resembled parvalbumin (PV) and somatostatin (SST) expressing interneurons. Using simulations and mathematical analyses, we show that the resulting circuit can be understood as a neural decoder that inverts the nonlinear biophysical computations performed within the pyramidal cells. Our model provides a proof of concept for studying structure-function relations in cortical circuits by a combination of gradient-based optimization and biologically plausible phenomenological models.

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