UCLA

Adequate perisomatic inhibition in the cortex, as supplied by parvalbumin-expressing (PV) inhibitory neurons, is fundamental to critical period plasticity and cortical function. Yet, how perisomatic inhibition emerges just at the inception of the critical period to shape the structure and function of cortical circuits is little understood. We report that PTEN in PV cells serves as a regulator of perisomatic inhibition by controlling the expression of EphB4, an inhibitor of PV to pyramidal inhibitory synapse formation. This points to a molecular disinhibitory mechanism for the initiation of the critical period, whereby sensory experience acts on PTEN in PV cells to decrease EphB4 expression in order to reduce the native repulsion between PV presynaptic terminals and pyramidal neuron cell bodies. This would then permit the formation of adequate perisomatic inhibition in cortical circuits. Given the compelling link between deficits in cortical perisomatic inhibition and various psychiatric disorders, such as autism spectrum disorders and schizophrenia, our findings also recommend EphB4 in PV cells as a novel target of therapy.