The role of perineuronal nets for spatial representations of the hippocampus

Abstract

Hippocampus is a brain region known to be important for memory and learning which requires a high level of plasticity throughout life. Perineuronal nets (PNNs) are specialized extracellular matrix structures found to condense around some types of neurons and have been suggested to stabilize synapses and limit plasticity. Experimental disruption of PNNs dramatically increases the level of plasticity in sensory cortices of adult animals. However, it remains elusive if the intact structure of PNNs is essential to higher cognitive functions such as spatial memory processing in the hippocampus. This study investigates how disruption of PNNs affects the place code of hippocampal place cells. Place cells display highly specific activity patterns in restricted areas of an animals environment, and are believed to encode spatial memories. The enzyme Chondroitinase ABC (chABC) which cleaves and dissembles the PNN structures, was injected into the dorsal areas of rat hippocampus and combined with electrophysiological large-scale recordings of place cells in awake and behaving animals. In order to elucidate how removal of the PNNs affects the spatial firing patterns of place cells, we recorded place cells from rats exploring a familiar and a novel environment. We found no apparent distortion of the place cells firing properties when chABC-injected animals were exploring a familiar environment. However, when the animals encoded information from a novel environment, a process that likely requires plasticity, the firing rates of place cells from chABC-injected animals were reduced compared to controls. Furthermore, the spatial information of place fields was enhanced in chABC animals compared to controls. The time for establishment of novel spatial representations was similar between groups. However, a decrease in the stability of place cell firing patterns over time was observed for chABC-injected animals. The results presented in this thesis suggest that PNNs could affect hippocampal place cell properties during encoding of a novel environment. Furthermore, we found low levels of PNN expression in the hippocampus compared to overlaying cortical areas. This may suggest that low expression of PNNs supports the high level of plasticity in the hippocampus.