Activity-dependent expression of Fezf2 regulates inhibitory synapse formation

The amount of inhibition a given neuron receives is dependent on its neuronal type. Additionally, neurons can regulate the amount of inhibition they receive through activity-dependent regulation of gene expression.

We use bulk sequencing of ribosome-associated RNA to show that selector gene Fezf2, which determines the specification of Layer 5 extratelencephalic (ET) projection neurons in utero, is regulated by neuronal activity. Postnatal reduction of Fezf2 expression decreases perisomatic inhibition originating from PV+ basket cells onto ET projection neurons, without affecting other hallmarks of ET neuron identity. We identify the type II Cadherin Cdh22 as a putative effector gene that is regulated both by FEZF2 and by neuronal activity, and removal of which decreases perisomatic inhibition.