TY - JOUR T1 - Cocaine Exposure Modulates Perineuronal Nets and Synaptic Excitability of Fast-spiking Interneurons in the Medial Prefrontal Cortex JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0221-18.2018 SP - ENEURO.0221-18.2018 AU - Megan L. Slaker AU - Emily T. Jorgensen AU - Deborah M. Hegarty AU - Xinyue Liu AU - Yan Kong AU - Fuming Zhang AU - Robert J. Linhardt AU - Travis E. Brown AU - Sue A. Aicher AU - Barbara A. Sorg Y1 - 2018/10/01 UR - http://www.eneuro.org/content/early/2018/10/01/ENEURO.0221-18.2018.abstract N2 - We previously reported that perineuronal nets (PNNs) are required for cocaine-associated memories. Perineuronal nets are extracellular matrix that primarily surrounds parvalbumin (PV)-containing, GABAergic fast-spiking interneurons (FSIs) in the medial prefrontal cortex (mPFC). Here we measured the impact of acute (1 day) or repeated (5 days) cocaine exposure on PNNs and PV cells within the prelimbic and infralimbic regions of the mPFC. Adult rats were exposed to 1 day or 5 days of cocaine and stained for PNNs (using Wisteria floribunda agglutinin, WFA) and PV intensity 2 h or 24 h later. In the prelimbic and infralimbic PFC, PNN staining intensity decreased 2 hr after 1 day of cocaine but increased after 5 days of cocaine. Cocaine also produced changes in PV intensity, which generally lagged behind that of PNNs. In the prelimbic PFC, both 1 and 5 days of cocaine increased GAD65/67 puncta near PNN-surrounded PV cells, with an increase in the ratio of GAD65/67:VGluT1 puncta after 5 days of cocaine exposure. In the prelimbic PFC, slice electrophysiology studies in FSIs surrounded by PNNs revealed that both 1 and 5 days of cocaine reduced the number of action potentials 2 h later. Synaptic changes demonstrated that 5 d cocaine increased inhibition of FSIs, potentially reducing the inhibition of pyramidal neurons and contributing to their hyperexcitability during relapse behavior. These early and rapid responses to cocaine may alter network stability of PV FSIs that partially mediate the persistent and chronic nature of drug addiction.Significance Statement Parvalbumin-containing, FSIs control the inhibitory:excitatory balance in the adult CNS, and the majority of these are surrounded by PNNs. The mPFC is critical to relapse in cocaine addiction, yet few studies have focused on the impact of cocaine exposure on PV interneurons that profoundly control output of the mPFC. Our studies highlight the impact of cocaine on PV and PNN levels and intrinsic and synaptic properties of PNN-surrounded FSIs in the mPFC. These findings point to a key upstream mechanism by which FSIs may contribute to the consistently observed increase in mPFC excitatory output of pyramidal neurons that contribute to cocaine reinstatement, and they have broader implications for understanding how PNN-surrounded neurons may control aberrant learning processes involved in addiction. ER -