GABAergic interneurons play crucial roles in the regulation of neural activity in the cerebral cortex. In this Dual Lecture, Prof Oscar Marín and Prof Beatriz Rico will discuss several aspects of the formation of inhibitory circuits in the mammalian cerebral cortex. Prof. Marín will provide an overview of the mechanisms regulating the generation of the remarkable diversity of GABAergic interneurons and their ultimate numbers. Prof. Rico will describe the molecular logic through which specific pyramidal cell-interneuron circuits are established in the cerebral cortex, and how alterations in some of these connectivity motifs might be liked to disease.   Our web pages for reference: https://devneuro.org.uk/marinlab/ & https://devneuro.org.uk/rico/default

GABAergic interneurons play crucial roles in the regulation of neural activity in the cerebral cortex. In this Dual Lecture, Prof Oscar Marín and Prof Beatriz Rico will discuss several aspects of the formation of inhibitory circuits in the mammalian cerebral cortex. Prof. Marín will provide an overview of the mechanisms regulating the generation of the remarkable diversity of GABAergic interneurons and their ultimate numbers. Prof. Rico will describe the molecular logic through which specific pyramidal cell-interneuron circuits are established in the cerebral cortex, and how alterations in some of these connectivity motifs might be liked to disease.

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. 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

The establishment of synaptic connections is essential for normal brain function, yet the molecular mechanisms responsible for the precise connectivity of specific neural circuits remain largely unknown. Previous work has shown that the assembly of cortical circuits requires specific functions of molecular signalling complexes at different classes of synapses. In this talk, I will describe the molecular logic through which specific pyramidal cell-interneuron circuits are established in the cerebral cortex of the mouse, and how alterations in some of these connectivity motifs might be liked to disease.

Inhibitory interneurons come in different classes and form intricate circuits. While our knowledge of these circuits has advanced substantially over the last decades, it is not fully understood how the structure of these circuits relates to their function. I will present some of our recent attempts to “understand” the structure of interneuron circuits by means of computational modeling. Surprisingly (at least for us), we found that prominent features of inhibitory circuitry can be accounted for by an optimisation for excitation-inhibition (E/I) balance. In particular, we find that such an optimisation generates networks that resemble mouse V1 in terms of the structure of synaptic efficacies between principal cells and parvalbumin-positive interneurons. Moreover, an optimisation for E/I balance across neuronal compartments promotes a functional diversification of interneurons into two classes that resemble parvalbumin and somatostatin-positive interneurons. Time permitting, I may briefly touch on recent work in which we link E/I balance to prediction error coding in V1.