Assembly and organisation of inhibitory networks in the cerebral cortex

The function of neural networks in the mammalian cerebral cortex relies on the interaction between two main classes of neurons, excitatory projection neurons (pyramidal cells) and inhibitory neurons (interneurons). In these circuits, the output of excitatory neurons is fine-tuned and synchronised by the activity of interneurons. Recent work suggests that distinct classes of interneurons preferentially target pyramidal cells with specific projection patterns to gate information flows in cortical circuits, but the mechanisms controlling this sophisticated form of interneuron specialisation are unknown. The general goal of this project is to investigate the mechanisms through which interneurons target specific networks of pyramidal cells. To this end, we will use: (1) conditional rabies virus tracing to dissect the connectivity of specific populations of pyramidal cells, including their primary inhibitory inputs; (2) DREADD to examine the role of activity during assembly of specific interneuron-pyramidal cell networks; (3) unbiased screenings to identify genes that regulate cell-type specific wiring within interneuron-pyramidal cell networks; and (4) Loss (shRNA and CRISPR/Cas9) and gain (cDNA) of function approaches, combined with optogenetic interrogation, to analyse the role of candidate genes in vivo. Our research will shed light on the mechanisms orchestrating the formation of inhibitory circuits in the cerebral cortex.