Abstract
Inhibitory interneurons expressing parvalbumin (PV) are central to cortical network dynamics, generation of c oscillations, and
cognition. Dysfunction of PV interneurons disrupts cortical information processing and cognitive behavior. Brain-derived neurotrophic
factor (BDNF)/tyrosine receptor kinase B (trkB) signaling regulates the maturation of cortical PV interneurons but is also
implicated in their adult multidimensional functions. Using a novel viral strategy for cell-type-specific and spatially restricted
expression of a dominant-negative trkB (trkB.DN), we show that BDNF/trkB signaling is essential to the integrity and maintenance
of prefrontal PV interneurons in adult male and female mice. Reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal
cortex (mPFC) resulted in deficient PV inhibition and increased baseline local field potential (LFP) activity in a broad frequency
band. The altered network activity was particularly pronounced during increased activation of the prefrontal network and
was associated with changed dynamics of local excitatory neurons, as well as decreased modulation of the LFP, abnormalities that
appeared to generalize across stimuli and brain states. In addition, our findings link reduced BDNF/trkB signaling in prefrontal
PV interneurons to increased aggression. Together our investigations demonstrate that BDNF/trkB signaling in PV interneurons in
the adult mPFC is essential to local network dynamics and cognitive behavior. Our data provide direct support for the suggested
association between decreased trkB signaling, deficient PV inhibition, and altered prefrontal circuitry.
