Seaton, Adam
(2019)
An investigation of the role of the nucleus accumbens in the hippocampal learning-behaviour translation.
PhD thesis, University of Nottingham.
Abstract
The hippocampus is required for important types of rapid everyday learning, including place learning. However, the pathways via which hippocampal place learning is translated into behaviour remain to be determined. The intermediate hippocampus is critical for the hippocampal learning-behaviour translation and combines neural substrates of accurate place encoding with links to prefrontal and subcortical behavioural control sites, which may contribute to this translation. The nucleus accumbens (NAc) is a main candidate due to strong hippocampo-NAc projections that have been implicated in behaviour based on place memory (Chapter 1).
To examine the role of the NAc, we combined functional inhibition (via microinfusion of the GABA agonist muscimol) with measurements of behavioural performance based on hippocampus-dependent rapid place learning using the watermaze delayed-matching-to-place (DMTP) test. Electrophysiological (Chapter 2) and sensorimotor experiments (locomotor activity, startle response/prepulse inhibition) (Chapter 3) showed that muscimol (125-250ng/0.5 μl/side) reduced NAc neurone firing around the infusion site by about 50% and caused, if at all, only moderate sensorimotor effects. The open field locomotor experiments indicated that NAc functional inhibition impaired between-session open field habituation, a process that has been suggested to require hippocampal contextual learning and memory. Our first watermaze experiment (Chapter 4), testing the impact of NAc muscimol within-subjects, supported that the NAc is required for DMP performance; however, there appeared to be a carry-over effect, with NAc muscimol eroding the typical DMTP search strategy on subsequent test days, possibly reflecting that NAc is required to reinforce the strategy. A second watermaze experiment (Chapter 5), using a between-subjects design, confirmed that NAc muscimol impairs expression of hippocampus-dependent rapid place learning on the DMP test, with a significant impairment of 1-trial place learning performance in the muscimol group on infusion days when compared to performance on washout days as reflected by reduced search preference for the correct location as compared to the saline group on infusions days, as well as by a significant impairment within the muscimol group, but not the saline group, on infusion days as compared to washout days.
Overall, these findings support that the NAc contributes to translation of rapidly-acquired place memory into behaviour as shown by performance impairment on the DMTP task following functional inhibition of the NAc. Beyond this, further investigation is required to demonstrate the direct hippocampal-NAc interaction.
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