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Title: Modulatory mechanisms involved in the neural processes of learning and memory in the rodent hippocampus
Author: Kearns, Ian R.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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The aim of this investigation was to examine the mechanisms implicated in the processes of learning and memory in the rodent hippocampus using electrophysiological recording techniques to monitor CA1 pyramidal cell activity. In the presence of ionotropic glutamate and g-aminobutyric acid (GABA) receptor antagonists, stimulation of the septohippocampal cholingeric afferents, in stratum oriens, produced a slow excitatory postsynaptic potential (EPSP). Subsequent pharmacological classification established that this response was mediated by activation of muscarine acetylcholine receptors (mAChR) and as such this response was termed an EPSPM. Specific blockers of voltage-gated Ca2+ channels, w-conotoxin GVIA and w-agatoxin IVA, revealed that the release of ACh necessary to evoke the EPSPM was mediated by activation of both N- and P/Q-type Ca2+ channels. Blockade of presynaptic 4-AP-senstivie K+ channels further enhanced the release of ACh. A previous report had shown that mAChR-mediated synaptic transmission could be modulated by adenosine A1 receptor activation but had not examined the precise cellular mechanisms underlying this effect. Investigations have revealed that the activation of A1 receptors inhibited the EPSPM irrespective of the Ca2+ channel supporting this response and that there maybe a partial involvement of 4-AP sensitive K+ channels. As adenosine A1 receptors are known to act via the G-protein, Gi/o, we also investigated the involvement of cAMP in the inhibition of the EPSPM. It was demonstrated that forskolin stimulated increases in cAMP partially occluded and 8-Br cAMP application fully occluded the adenosine A1 receptor-mediated inhibition of the EPSPM. Most synapses are under the regulation of a variety of GPCRs. In this respect we also demonstrated that opioid receptor agonists could modulate the EPSPM. Interestingly, it was found that opioid agonists acting at a presynaptic m-opioid receptor caused an enhancement of the EPSPM although the mechanism of how this is achieved is unclear.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available