Sarah E. Canetta (Primary Presenter); E. Teboul, A.S. Brown & C. Kellendonk

Abnormalities in prefrontal cortical parvalbumin-expressing (PFC PV) interneurons are believed to contribute to cognitive and affective deficits in schizophrenia, as well as other neurodevelopmental psychiatric disorders. However, little is known about whether developmental alterations in PV inhibitory interneuron maturation and integration into cortical circuitry could be contributing to disease onset. We have recently shown that mice exposed to an early environmental risk factor for schizophrenia—prenatal maternal immune activation (MIA)—show decreased functional inhibitory connectivity between PFC PV interneurons and pyramidal cells in adulthood, and that these physiological changes result in impairments in cognitive flexibility and anxiety. Therefore, we decided to utilize this model to investigate changes in PFC PV interneuron function during development that may precede and precipitate these long-term functional and behavioral alterations observed in the adult. We discovered that PFC PV interneurons in MIA offspring are transiently less excitable during early development, during a window in which both formation and pruning of inhibitory synaptic connections is known to occur. Our ongoing studies now aim to understand whether these transient changes in PFC PV interneuron excitability early in development are sufficient to induce the long-term changes in PFC PV interneuron functional connectivity, as well as cognitive and affective behavioral alterations, observed in adult MIA offspring.

This work was supported by the National Institute of Mental Health K01MH107760, Sackler Foundation Fellowship, and the Brain and Behavior Research Foundation Young Investigator Award.