Perineuronal nets in the entorhinal cortex and their role for the hippocampal place code

Abstract

The reciprocally connected entorhinal cortex and hippocampal formation (HF) are pivotal in spatial navigation and episodic memory. Principal neurons in these regions show spatially modulated activity with grid cells in the medial entorhinal cortex (MEC) most likely providing place cells in the HF with information about the animal’s position in the environment. The MEC is rich in perineuronal nets (PNNs), a type of extracellular matrix that wraps around the soma and proximal dendrites of neurons. The PNNs are in large thought to limit plasticity as removal of PNNs in adult animals induces plasticity to juvenile levels in e.g. the visual cortex. PNNs are particularly abundant around fast-spiking parvalbumin positive interneurons in the MEC, a class of inhibitory neurons which may synchronize activity within MEC and contribute to convey information transfer between the MEC and the HF. The role of the PNNs in the MEC remains unknown. This thesis addresses this by investigating the effects of PNN removal in the MEC on the spatial representations of hippocampal of place cells. The PNNs were degraded by local injections of the enzyme chondroitinase (chABC), which cleaves the extracellular matrix, into the MEC of adult rats. By means of chronically implanted tetrodes, single unit activity and local field potentials were recorded simultaneously from the dorsocaudal part of the MEC and the dorsal CA1 and CA2 of the HF. In order to compare states involving different levels of plasticity, recordings were conducted from animals in both familiar and novel environments. While CA2 place cells were largely unaffected by the chABC treatment, there was a pronounced effect on CA1 place cells with increased firing rates, larger place fields, decreased spatial information, and sparseness scores in the familiar environment. Furthermore, spatial representations in CA1 place cells were observed to be less stable across sessions in the same room. CA2 place cells were largely unaffected by the treatment. Taken together, this suggest that PNNs in MEC might play a role in stabilizing spatial representations in hippocampal CA1 place cells, and that the effects are more pronounced in familiar rooms. In addition, the different responses of CA1 and CA2 place cells suggest that input from MEC to the hippocampus may be differently weighted and processed in CA1 and CA2.