How are the mammalian cortical networks built?
The function of neural networks in the cerebral cortex of vertebrates relies on the interaction between two main classes of neurons, excitatory projection neurons and inhibitory interneurons. In these circuits, the output of excitatory neurons is fine-tuned and synchronised by the function of inhibitory neurons. Most notably, different classes of interneurons target different compartments of the pyramidal cells, the apical dendrites, the cell body, or even the axonal initial segment (AIS). Since the location of synaptic contacts largely determines their influence on the postsynaptic cell, it has been suggested that this elaborate organisation of inputs greatly increases the overall computational power of single neurons. One of the goals in my lab is to identify molecules involved in the formation of subcellular domain-restricted GABAergic synapses. To this end, we have carried out several unbiased genomic screens during comparing unique populations of interneurons that make synapses into different subcellular compartments. We have unveiled cell-specific molecular programs in cortical interneurons that emerge during the early wiring of these cells and underlie the specification of their connection patterns.
In addition to the molecular codes controlling the subcellular targeting of inhibitory synapses, interneurons precisely target different pyramidal cell subnetworks. We are currently investigating the cellular and molecular mechanisms underlying the assembly of these inhibitory circuitries. Unravelling the mechanisms that control the precise spatial organization of synapse formation during development should have a broad impact, from understanding plasticity in the healthy brain to identifying wiring abnormalities in disease.