CAUSAL LINKS BETWEEN PV+ INTERNEURON DEFICITS, ABERRANT GAMMA OSCILLATIONS AND SCHIZOPHRENIA SYMPTOMATOLOGY IN MICE

Schizophrenia is associated with impaired executive control and abnormal neural synchrony within prefrontal–hippocampal circuits. Alterations in parvalbumin-positive (PV⁺) interneurons are consistently implicated in the disorder; however, whether PV⁺ dysfunction alone is sufficient to induce circuit-level dyscoordination remains unclear. Here, we examine the causal impact of bidirectional PV⁺ interneuron modulation in the prelimbic cortex (PL) of the medial prefrontal cortex (mPFC) on oscillatory dynamics, cross-frequency coupling, and prefrontal–hippocampal communication. PV-Cre mice received bilateral Cre-dependent excitatory or inhibitory DREADDs targeting PV⁺ interneurons in PL. Following acute administration of the DREADD agonist JHU37160, we performed electrophysiological recordings in PL mPFC and CA1 dHPC and behavioral assays probing positive, negative, and cognitive symptoms relevant for schizophrenia. Neural analyses focus on band-limited power (theta/gamma/high frequencies), theta–gamma phase–amplitude coupling (PAC), interregional synchrony (weighted phase-lag index, wPLI), and directed connectivity (phase-slope index, PSI) between PL and CA1. By causally linking PV⁺ interneuron activity to prefrontal–hippocampal coordination, this work aims to clarify the circuit mechanisms underlying the distinct symptomatology in schizophrenia. Ongoing and future experiments will extend this approach to NMDA receptor hypofunction models to assess whether targeted PV⁺ modulation can normalize electrophysiological and behavioral abnormalities.