Removal of Perineuronal Nets in the Medial Prefrontal Cortex Impairs the Acquisition and Reconsolidation of a Cocaine-Induced Conditioned Place Preference Memory

Abstract

Pyramidal neurons in the medial prefrontal cortex (mPFC) critically contribute to cocaine-seeking behavior in humans and rodents. Activity of these neurons is significantly modulated by GABAergic, parvalbumin-containing, fast-spiking interneurons, the majority of which are enveloped by specialized structures of extracellular matrix called perineuronal nets (PNNs), which are integral to the maintenance of many types of plasticity. Using a conditioned place preference (CPP) procedure, we found that removal of PNNs primarily from the prelimbic region of the mPFC of adult, male, Sprague Dawley rats impaired the acquisition and reconsolidation of a cocaine-induced CPP memory. This impairment was accompanied by a decrease in the number of c-Fos-positive cells surrounded by PNNs. Following removal of PNNs, the frequency of inhibitory currents in mPFC pyramidal neurons was decreased; but following cocaine-induced CPP, both frequency and amplitude of inhibitory currents were decreased. Our findings suggest that cocaine-induced plasticity is impaired by removal of prelimbic mPFC PNNs and that PNNs may be a therapeutic target for disruption of cocaine CPP memories.

The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference

“…Changes in PNNs have been shown to affect the firing properties of PV cells, thereby influencing GABAergic control over pyramidal cell activity (Dityatev et al, 2007). Indeed, in the mPFC, degradation of PNNs results in reduced inhibitory input onto pyramidal cells and this impairs acquisition of cocaine CPP memory (Slaker et al, 2015). However, overexpression of brevican in the mPFC of Bcan +/ − mice did not prevent incubation of cocaine memory, and virally expressed brevican in the dHPC did not preferentially co-localize with PV cells and PNNs, hinting to a mechanism that does not specifically involve PNNs.…”

Signals from the Fourth Dimension Regulate Drug Relapse

“…Degradation of PNNs in the prelimbic PFC reduces acquisition and reconsolidation without affecting the rate of extinction or spontaneous recovery of cocaine-induced CPP [113]. These authors also demonstrate that depletion of PNNs in the prelimbic PFC reduces inhibitory drive onto pyramidal neurons while enhancing intrinsic excitability [113]. …”

“…Also when combined with extinction training, intra-amygdala injections of Ch-ABC enhanced expression of plasticity-related proteins (i.e., BNDF and AMPA receptors) [112]. Degradation of PNNs in the prelimbic PFC reduces acquisition and reconsolidation without affecting the rate of extinction or spontaneous recovery of cocaine-induced CPP [113]. These authors also demonstrate that depletion of PNNs in the prelimbic PFC reduces inhibitory drive onto pyramidal neurons while enhancing intrinsic excitability [113].…”

Modelos animales de adicción a las drogas

“…En estos estudios, los animales adquieren el CPL de forma habitual, después se reactivan las memorias de la droga (exponiendo a los animales al compartimento asociado a la droga durante el condicionamiento por un breve período de tiempo) y tras un breve intervalo (de 10 min a 2 horas) se les somete a sesiones de extinción del CPL o a algún tratamiento amné-sico. Estas manipulaciones producen una rápida extinción de la respuesta condicionada y previenen la aparición de la reinstauración del CPL tras la exposición a un priming de droga (Liu et al, 2015;Lv, Sun, Cui y Han, 2015;Miller y Marshall, 2005;Slaker et al, 2015).…”