Characterisation of dentate gyrus in a freely moving mouse expressing a population of mutant NMDA receptors

• Main Author: Burton, S.
• Other Authors: O'Keefe, J.
• Published: University College London (University of London) 2013
• Subjects: 570
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.626197

Hippocampal LTP induction is dependent on the activity of the glutamate receptor N-Methyl-D-Aspartate (NMDA) and may provide the basis for long-term memory (Bliss and Collingridge, 1993). (Chen et al., 2009) have created a genetically modified mouse model expressing a gain of function of the Grin1N598R allele that produced a reduction (approximately 10 %) of functional NMDA receptors throughout the brain. Early long term potentiation (LTP) in these mice was completely blocked in the perforant path/dentate gyrus synapse, though unaffected in Schaffer collaterals/CA1 synapses of the hippocampus. These electrophysiological disparities were accompanied by behavioural impairments in place recognition and place learning in the Morris water maze. In this thesis I describe the effects of this mutation on spatially modulated cells of the hippocampal CA1 and the dentate gyrus during exploration of familiar and novel environments. No electrophysiological differences were observed in the firing of mutant CA1 place cells. In contrast, the spatial tuning and the stability of dentate granule cells were compromised in the mutant mice. The majority of isolated cells in the control mice formed spatially specific firing patterns whereas the mutant mice cells mainly formed random activity patterns. Trial-to-trial stability was superior in control mice and a greater percentage of cells were theta modulated. In agreement with recent work (Neunuebel and Knierim, 2012), the majority of dentate place cells formed single place fields in contrast to previous reports of multiple fields in the rat (Jung and McNaughton 1993, Leutgeb et al., 2007).