THE EFFECTS OF DEGRADING PERINEURONAL NETS IN THE MEDIAL PREFRONTAL AND POSTERIOR PARIETAL CORTICES ON THE SPATIAL WORKING MEMORY OF RATS

Abstract

Perineuronal nets (PNNs) are specialized extracellular matrix structures that surround subsets of neurons in the central nervous system (CNS). They help in maintaining a stable excitatory-inhibitory balance in the brain, and the adult loss of PNNs can lead to a period of increased synaptic plasticity. Furthermore, the loss of PNNs can affect cortical networks and influence learning, memory, and cognition. The aim of this thesis was to test the effect that degrading PNNs in the medial prefrontal (mPFC) and posterior parietal (PPC) cortices had on spatial working memory (WM). To do this, the spatial WM of Long-Evans rats was measured using the trial unique, delayed nonmatching-to-location (TUNL) task in touchscreen-equipped operant conditioning chambers. Rats were trained in this task and then assigned to either a penicillinase (PEN) control or chondroitinase ABC (ChABC) treatment. ChABC is an enzyme that compromises the structure of PNNs by degrading one of their major components: chondroitin sulfate proteoglycans (CSPGs). Surgeries were performed to infuse these enzymes into the medial prefrontal cortex (mPFC) in a first set of rats and into the posterior parietal cortex (PPC) in a second set of rats. All rats were trained under a standard 6 s delay and then tested under 4 conditions: a 6 s delay, a variable 2 s or 6 s delay, a 2 s delay with a 1s inter-trial interval (interference condition), and a 20 s delay. Rats that received mPFC ChABC infusions initially performed better than controls in the 20 s delay condition, but did not perform any differently in any of the other three conditions. Rats that received PPC ChABC infusions did not perform significantly differently from controls in any condition. Immunohistochemical analysis confirmed that CSPGs were degraded in both cortical regions. This suggests that PNNs in the mPFC are involved in learning a novel delay in a spatial WM task, but that they are not essential for general spatial WM function. Furthermore, it appears that PNNs in the PPC are not involved in spatial WM. Ultimately, these findings contribute to a growing body of literature that explores how cortical PNNs are involved in cognition.