Excess dopamine D2R activation accounts for PV+ basket cell and learning alterations in mouse model of schizophrenia

Schizophrenia is consistently associated with alterations in parvalbumin-positive basket cell functions, and with reduced gamma power of network activity, but causal relationships between PV dysfunctions and clinical manifestations of schizophrenia have remained unclear. Here I investigated LgDel+/- mice, a genetic model closely reproducing chromosomal deletions in 22q11 patients. I found that early-born PV interneurons are specifically affected in the LgDel+/- mice, suggesting a specific deficit in synaptic excitation of PV neurons. The PV alterations were associated with specific deficits in long-term memory consolidation and in top-down executive control. Delivery of the D2-receptor antagonist haloperidol to mutant mice rescued PV network alterations and long-term memory. My findings are consistent with the notion that PV network deregulation has an important role in cognitive deficits of schizophrenia model mice.