Optimizing interneuron circuits for compartment-specific feedback inhibition

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.Author summary: The brain contains billions of nerve cells—neurons—that can be classified into different types depending on their shape, connectivity and activity. A particularly diverse group of neurons is that of inhibitory neurons, named after their suppressive effect on neural activity. Presumably, their diverse properties allow inhibitory neurons to fulfil different functions, but what these functions are is currently unclear. In this paper, we investigated if a particular function can explain the existence and properties of the two most common inhibitory cell classes: The need to regulate activity in different physical parts (compartments) of the neurons they target. We investigated this function in a computer model, using optimization to find the neuron properties best-suited for compartment-specific inhibition. Our key result is that after the optimization, model neurons largely fell into two classes that resembled the two types of biological neurons. In particular, the optimized neurons were connected to only one compartment of other neurons. This suggests that the diversity of inhibitory neurons is well suited for compartment-specific inhibition. In the future, our approach of optimizing neural properties might be used to investigate other functions (or dysfunctions) of neuron diversity.