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Title: Adenosinergic modulation of glutamate release in the rat hippocampus
Author: Robinson, Katherine A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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Presynaptic adenosine A1 receptors, at synapses between Schaffer collateral commissural (SCC) fibres and hippocampal CA1 neurones, were studied using the whole cell blind patch clamp technique and determining the effects of an adenosine agonist and antagonist. The selective adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) and the antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) had no effect on the apparent input resistance (Rm) and membrane potential (Em) of the postsynaptic cell and thus unlikely to alter the magnitude of synaptic response postsynaptically. Two approaches were employed to examine the role of the adenosine A1 receptor in the regulation of glutamate release. Firstly, spontaneous miniature EPSPs (mEPSPs) were recorded and the actions of either CCPA or DPCPX were studied. Neither drug altered the mean amplitude of the mEPSPs compared to control. CCPA decreased the frequency of the mEPSPs from control, an inhibition which was completely reversed by co-application of DPCPX DPCPX alone increased the mean frequency of the mEPSPs from control. This suggested that the CA-1 neurones are subject to a tonic inhibition by endogenous adenosine. Secondly, single and pairs of evoked responses were measured during the activation of the SCC fibres using low intensity stimulation before and after exposure to either CCPA or DPCPX. After exposure to DPCPX the amplitude distributions of the singly evoked EPSPs and EPSCs were significantly shifted to the right when compared to control. This was accompanied by an increase in the mean amplitude. In paired pulse experiments, carried out under current and voltage clamp, exposure to CCPA produced a leftwards shift in the amplitude distributions of both the EPSPs and EPSCs and significantly decreased the mean amplitude of both the first and second responses. After exposure to DPCPX the mean amplitude of the EPSPs and EPSCs increased, but not significantly, and their distribution was shifted to the right.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available