Abstract
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 d) or repeated (5 d) cocaine exposure on PNNs and PV cells within the prelimbic and infralimbic regions of the mPFC. Adult rats were exposed to 1 or 5 d of cocaine and stained for PNNs (using Wisteria floribunda agglutinin) and PV intensity 2 or 24 h later. In the prelimbic and infralimbic PFC, PNN staining intensity decreased 2 h after 1 d of cocaine exposure but increased after 5 d of cocaine exposure. Cocaine also produced changes in PV intensity, which generally lagged behind that of PNNs. In the prelimbic PFC, both 1 and 5 d of cocaine exposure increased GAD65/67 puncta near PNN-surrounded PV cells, with an increase in the GAD65/67-to-VGluT1 puncta ratio after 5 d of cocaine exposure. In the prelimbic PFC, slice electrophysiology studies in FSIs surrounded by PNNs revealed that both 1 and 5 d of cocaine exposure reduced the number of action potentials 2 h later. Synaptic changes demonstrated that 5 d of cocaine exposure increased the 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 the network stability of PV FSIs that partially mediate the persistent and chronic nature of drug addiction.
Highlights
Pyramidal neurons in the medial prefrontal cortex that project to the nucleus accumbens control cocaine-seeking behavior in rodent models of addiction (McFarland and Kalivas, 2001; McLaughlin and See, 2003; McFarland et al, 2004; Ma et al, 2014)
We show the locomotor activity of every rat used in these studies after acute and repeated saline or cocaine exposure, the latter of which produces behavioral sensitization (Robinson and Berridge, 1993)
Here we demonstrated that the intensity of perineuronal nets (PNNs) and PV rapidly decreases in the prelimbic and infralimbic PFC following a novel cocaine exposure but increases following repeated cocaine exposure
Summary
Pyramidal neurons in the medial prefrontal cortex (mPFC) that project to the nucleus accumbens control cocaine-seeking behavior in rodent models of addiction (McFarland and Kalivas, 2001; McLaughlin and See, 2003; McFarland et al, 2004; Ma et al, 2014). Surprisingly few studies (Kroener and Lavin, 2010; Campanac and Hoffman, 2013) have examined the impact of cocaine on fast-spiking GABAergic interneurons, which contain parvalbumin (PV; Kawaguchi and Kubota, 1993). Several studies have demonstrated an important contribution of PNNs to learning and memory (Balmer et al, 2009; Fawcett, 2009; Gogolla et al, 2009; Romberg et al, 2013; Banerjee et al, 2017; Foscarin et al, 2017). We previously found that the consolidation and reconsolidation of cocaine-associated memories were dependent on intact PNNs in the mPFC (Slaker et al, 2015), and others have reported a role for PNNs in drug-related behaviors (Van den Oever et al, 2010b; Xue et al, 2014; Vazquez-Sanroman et al, 2015b)
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