Disrupted-in-Schizophrenia-1 is required for proper pyramidal cell-interneuron communication and network dynamics in the prefrontal cortex

We interrogated prefrontal circuit function in mice lacking Disrupted-in-schizophrenia-1 (Disc1-mutant mice), a risk factor for psychiatric disorders. Single-unit recordings in awake mice revealed reduced average firing rates of fast-spiking interneurons (INTs), including optogenetically identified parvalbumin-positive cells, and a lower proportion of INTs phase-coupled to ongoing gamma oscillations. Moreover, we observed decreased spike transmission efficacy at local pyramidal cell (PYR)-INT connections in vivo , suggesting a reduced excitatory effect of local glutamatergic inputs as a potential mechanism of lower INT rates. On the network level, impaired INT function resulted in altered activation of PYR assemblies: While assembly activations were observed equally often, the expression strength of individual assembly patterns was significantly higher in Disc1-mutant mice. Our data thus reveal a role of Disc1 in shaping the properties of prefrontal assembly patterns by setting prefrontal INT responsiveness to glutamatergic drive.