Cocaine memory reactivation induces functional adaptations of fast-spiking interneurons in the rat medial prefrontal cortex

Jorgensen, E. T.; Gonzalez, A. E.; Harkness, J. H.; Hegarty, D. M.; Burchi, D. J.; Aadland, J. A.; Aicher, S. A.; Sorg, B. A.; Brown, T. E.

doi:10.1101/868299

bioRxiv · 10.1101/868299

Cocaine memory reactivation induces functional adaptations of fast-spiking interneurons in the rat medial prefrontal cortex

Jorgensen, E. T.·Gonzalez, A. E.·Harkness, J. H.·Hegarty, D. M.·Burchi, D. J.·Aadland, J. A.·Aicher, S. A.·Sorg, B. A.·Brown, T. E.

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Abstract

Perineuronal nets (PNNs) are specialized extracellular matrix structures that ensheathe parvalbumin-containing fast-spiking interneurons (PV FSIs) and play a key role in neuroplasticity. We previously showed that PNNs within the prelimbic prefrontal cortex (PL PFC) are required for the maintenance of cocaine-associated memories following cocaine memory reactivation. However, how cocaine memory reactivation affects PNNs, PV, and corresponding changes in PV FSI function are unknown. In this study, we characterized the electrophysiological properties of PV FSIs and corresponding changes in PNN and PV intensity within the PL PFC prior to and after cocaine memory reactivation. Adult male Sprague-Dawley rats were trained to acquire cocaine-conditioned place preference (CPP) and, following cocaine-CPP memory reactivation (30 m, 2 h, and 24 h post-reactivation), we measured PNN intensity (determined by Wisteria floribunda agglutinin [WFA] staining) as well as PV intensity using immunohistochemistry. The intensity of PV staining was reduced at all time points following memory reactivation with no changes in WFA intensity. Using whole-cell electrophysiology we found a reduction in the number of action potentials at 30 m and 2 h that returned to control levels by 24 h. The attenuation in firing was accompanied by a presumed compensatory increase in excitatory synaptic transmission, which was corroborated by an increase in VGluT1 puncta apposing PV/PNN neurons. Collectively, our results indicate that cocaine memory reactivation decreases PV intensity, which may play a role in decreasing excitation of PV FSIs. Thus, the inhibitory tone onto pyramidal neurons may be decreased following memory reactivation, resulting in an increase in PFC output to promote cocaine-seeking behaviors.

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Jorgensen, E. T., Gonzalez, A. E., Harkness, J. H., Hegarty, D. M., Burchi, D. J., Aadland, J. A., Aicher, S. A., Sorg, B. A., Brown, T. E.. 2019-12-06. Cocaine memory reactivation induces functional adaptations of fast-spiking interneurons in the rat medial prefrontal cortex. https://doi.org/10.1101/868299

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