CAUGHT IN THE NET: PERINEURONAL NETS  AND COCAINE MEMORY

Megan L. Slaker

Perineuronal nets (PNNs) are aggregations of extracellular matrix molecules that form net-like structures around the perimeter of a subset of neurons within the central nervous system. PNNs appear during development in an experience-dependent manner, and their appearance coincides with the closure of critical periods during which neuronal systems are highly malleable and influenced by external stimuli. During adulthood, PNNs regulate plasticity and are continually modulated by experience. Within this body of work, the relationship between PNNs, drugs of abuse, and memory was investigated in rats. The central hypothesis was that PNNs within the prefrontal cortex (PFC) dynamically change in response to drug exposure and are integral for the formation and persistence of drug-associated memories that underlie relapse. The PFC is involved in drug-seeking behavior, memory, and drug-associated memories. To test this hypothesis, PNNs within the PFC were removed to target different stages of drug-associated memory. Removal of PNNs disrupted both initial formation and reconsolidation of drug-associated memories. Next, a method of PNN staining intensity quantification was developed to assess the dynamic nature of PNNs. Several studies suggest that PNN staining is inversely related to plasticity; for example, as PNN staining decreases, the potential for plasticity increases. Our novel method of PNN staining intensity analysis allows for standardization and automation. Using this method of PNN staining intensity quantification, we examined PNNs after several behavioral manipulations. Following sucrose self-administration and exposure to environmental enrichment (EE), PNN staining intensity increased within several regions of the PFC, suggesting that EE decreased the potential for plasticity. Following acute novel EE exposure in rats without a history of sucrose self-administration, PNNs were altered in a region-dependent manner. Finally, PNNs within the PFC dynamically respond to cocaine exposure in a time- and region-dependent manner. Taken together these studies indicate that PNNs are dynamic structures that respond to environmental manipulations and are necessary for drug-associated memory formation and maintenance. These findings have implications for understanding of how drug-induced plasticity and cocaine-associated memories may be manipulated to diminish relapse.

CAUGHT IN THE NET: PERINEURONAL NETS AND COCAINE MEMORY

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