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The role of the GluN2A NMDAR subunit in hippocampal function

We have generated a new rodent model to study the functional role of the GluN2A NMDAR subunit by employing CRISPR/Cas9 gene editing methods to generate a transgenic rat line in which exon 8 of the Grin2A gene is deleted – this results in complete loss of expression of GluN2A protein in homozygote Grin2A-/- animals.

GluN2A subunits together with GluN2B subunits are the most abundantly expressed NMDAR subunits in the mammalian forebrain.  This project will utilize this novel model to investigate the role GluN2A subunits play in two aspects of hippocampal function that depend on NMDAR-mediated synaptic plasticity: hippocampus-dependent memory, and hippocampal place cell stability.  Hippocampal NMDARs are required to form lasting object-place (OP) associations in spontaneous exploration tasks [1] although the NMDAR subtype dependency of this learning remains unknown.  The first aim of the project will be to determine whether rats lacking GluN2A NMDARs are able to form OP and other hippocampus-dependent memories [2]. In the second part of the project, the role of GluN2A NMDARs in encoding space will be examined.  Specifically the project will assess the extent to which place fields “learn” to fire in a constant location with respect to environmental cues - a property known to be disrupted by NMDAR antagonists [3] - in rats lacking GluN2A subunits. This part of the project will use in vivo extracellular recording techniques single neurons to characterise place cell activity using protocols similar to those we have used previously [4] and will compare basic place cell properties (firing rate, spatial information), and the development and stability of place fields during the first and subsequent exposures to novel environments.

References

  1. Barker GR & Warburton EC (2015). Cereb Cortex, 25, 472-481.
  2. Langston RF & Wood ER (2010). Hippocampus, 20, 1139-1153.
  3. Kentros C et al. (1998) Science, 280, 2121-2126.
  4. Bett D et al. (2013). J Neurosci, 33, 6928-6943.

Primary co-supervisor

Prof David Wyllie

Prof David Wyllie lab

+44 (0)131 650 4564

david.j.a.wyllie@ed.ac.uk

Primary co-supervisor

Dr Emma Wood

Dr Emma Wood lab

+44(0) 131 650 3531

Emma.Wood@ed.ac.uk