biostudies-literatureSauer JFDeutsche ForschungsgemeinschaftEuropean Research Councile79471https://www.ebi.ac.uk/biostudies/studies/S-EPMC9566853biostudies-literatureUnknown11We interrogated prefrontal circuit function in mice lacking <i>Disrupted-in-schizophrenia-1</i> (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 defined as coactivations within 25 ms 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 INT responsiveness to glutamatergic drive.eLife<i>Disrupted-in-schizophrenia-1</i> is required for normal pyramidal cell-interneuron communication and assembly dynamics in the prefrontal cortex.PMC9566853787450ERC-AdG787450FOR2143-2FOR5159 TP7BA1582/2-2SA3609/1-1Sauer JFBartos Mfalse<i>Disrupted-in-schizophrenia-1</i> is required for normal pyramidal cell-interneuron communication and assembly dynamics in the prefrontal cortex.We interrogated prefrontal circuit function in mice lacking <i>Disrupted-in-schizophrenia-1</i> (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 defined as coactivations within 25 ms 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 INT responsiveness to glutamatergic drive.2022-01-01T00:00:00Z2022 Oct2025-04-26T22:09:05.565Z2025-04-06T17:04:52.556ZS-EPMC95668533623998810.7554/eLife.79471