In this thesis, I describe the use of two different techniques for the targeting and functional inactivation of individual populations of GABAergic interneurons located within the cerebellum and dentate gyrus of the hippocampus. Through functional inactivation of these interneuron types, I demonstrate their behavioural relevance for the processes of learning and memory. In chapter 2, I describe a genetic approach for the removal of GABAA-mediated signalling from molecular layer interneurons (MLIs) onto Purkinje cells within the cerebellum. Using the Cre lox P system to delete post-synaptic GABAA receptors on Purkinje cells, I have shown a previously unappreciated role for MLIs in fear memory. Deficits were specific to the acquisition and long-term retention of fear memories suggesting that feed-forward inhibition from MLIs onto Purkinje cells is critical for these processes. In chapter 3, I describe a further development to this project through the creation of a novel dual recombinase mouse line. This intersectional approach of combining Cre and Flpo recombinase systems together would allow direct targeting of MLIs for the first time and circumvent drawbacks associated with using a static genetic knockout approach. In chapter 4, I describe an adeno-associated viral (AAV) approach to target a specific population of GABAergic interneurons located within the hilar region of the dentate gyrus. These hilar perforant path-associated (HIPP) cells are characterised by their expression of the neuropeptide somatostatin (SST) and regulate granule cell activity through feedback inhibition. However, up until now their behavioural relevance has been unknown. Through Cre-mediated viral expression of tetanus toxin light chain (TeLC), neurotransmission was prevented in SST interneurons revealing an involvement in spatial working memory and spatial reference memory precision. In addition, preliminary immediate early gene data suggests that SST interneurons increase memory precision through maintaining the sparse activity of the granule cell population through feedback inhibition.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:571686 |
| Date | January 2012 |
| Creators | Cole, Katherine L. H. |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=192220 |
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