The effects of Morris water maze learning on the number, morphology and molecular composition of rat hippocampal dentate gyrus synapses

Eyre, Mark David (2003). The effects of Morris water maze learning on the number, morphology and molecular composition of rat hippocampal dentate gyrus synapses. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000f709

Abstract

spatial long-term memory formation is dependent upon the hippocampus and associated brain structures in mammals. Memory storage is believed to involve changes in the way information is exchanged between neurons, and this is principally governed by their synaptic connections. Changes can occur in the functional properties of individual synapses, but evidence suggests that morphological changes may also occur. Research described in this thesis has used the Morris water maze, a behavioural paradigm that requires rodents to form long-term memories about a spatial environment, and this learning task involves the function of the hippocampus. Electron microscopy was used to investigate the ultrastructural morphology and composition of synapses in the hippocampal dentate gyrus in several groups of animals. Three time- points were investigated, 3, 9 and 24 hours after the start of training, which also corresponded to small, intermediate and large amounts of training, as well as two different types of control, naïve and swim-only. Animals investigated 3 hours after the start of training did not show significant long term memory for the task, whereas animals investigated 9 and 24 hours after the start of learning displayed long-term memory recall when measured by the quadrant analysis test (probe trial). Hippocampal dimensions and dentate granule cell densities were similar between all animal groups.

No significant changes to synaptic ultrastructural morphology were evident in the 3 hour group. In the 9 hour group, significant increases in synapse density and synapse to neuron ratio were observed, with a simultaneous decrease in the synapse mean height and average area of PSD (post-synaptie density) per synapse. No significant changes were observed in the exercise-matched swim-only controls, suggesting that the changes were related to long-term memory formation. Morphological changes were not evident in the 24 hour group, despite long term memory recall, suggesting that the morphological changes following spatial learning in the Morris water maze are transient. The total amount of synaptic membrane was not significantly different between any of the groups, suggesting that although new, smaller synapses may be formed as a result of learning, changes also occur to existing synapses, which may result in their re-categorisation or even removal. Analysis of ionotropic glutamate receptors following training proved inconclusive, particularly for NMDA receptors, but did suggest that AMP A receptors are increased in the initial stages of learning, which may be a mechanism of short-term memory storage.

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