Perineuronal nets define two functionally distinct Parvalbumin Interneuron subpopulations in the medial prefrontal cortex

Perineuronal nets (PNNs) are a fundamental component of cortical synapses regulating synaptic plasticity and circuit function. PNNs form during postnatal development and their alteration is linked to neurodevelopmental disorders. Although PNNs surround multiple cortical neurons, parvalbumin-positive interneurons (PVI) are the cell type most associated with them. PVI provide the main inhibitory drive to pyramidal neurons, supporting E/I balance and gamma oscillations, and PNNs shape their plasticity. Unlike sensory cortices, the mPFC shows fewer PVI with well-developed PNNs, suggesting high- and low-PNN subpopulations with distinct properties. We asked whether PNN status defines functionally distinct PVI subpopulations in adult mouse mPFC, acting as low-plasticity gain-control or high-plasticity dynamic units. WFA labeling revealed three PNN-intensity populations (174 PVI, 7 mice), split at the median into high- and low-PNN groups. Whole-cell recordings showed low-PNN PVI had greater excitability, higher input resistance, longer time constant, lower rheobase, larger AHP, and higher maximal firing rate than high-PNN PVI. Theta-burst stimulation induced long-term potentiation of EPSPs selectively in low-PNN, not high-PNN, PVI. These results show PNN density delineates PVI subpopulations with distinct intrinsic and plasticity properties in the mPFC, potentially forming segregated subcircuits. Ongoing work extends this to an NMDA receptor ablation model relevant to schizophrenia.