Final Report Summary - SYNAPDOMAIN (Molecular Mechanisms of GABAergic synapse formation: spatial segregation in cortical inhibitory inputs)
Understanding brain function and dysfunction begins with the knowledge of how neuronal connections are established and organized in functional networks. The remarkable diversity and connectivity patterns of cortical interneurons, place them in a unique position to orchestrate functionally relevant circuit-specific roles and critically shape cortical function. Consistently, GABAergic dysfunction has been implicated in several neurological and psychiatric disorders. While some progress has been made towards understanding the molecular and structural components that broadly distinguish inhibitory synapses and their assembly, the molecular mechanisms underlying interneuron subtype-specific assembly are largely unknown. During the development of this project, we have discovered: 1) An extracellular protein that is gating the parvalbumin interneuron function by controlling the number of somatic outputs they receive; 2) a tyrosine kinase receptor that is regulating the synapses of a specific interneuron subclass; 3) A kinase that coordinates the wiring of parvalbumin interneurons; 4) the transcriptional dynamics of a sample of interneurons with a restricted targeting area into the pyramidal cells, the dendritic, somatic and axonal initial segment compartments (AIS) during synapse formation and we identified cell-specific molecular signatures supporting interneuron early wiring and underlying the specification of different patterns of connectivity.