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Adenosinergic modulation of hippocampal gamma oscillations: from single cell to whole animal

Pietersen, Alexander Nicolaas Johannes (2010)
Ph.D. thesis, University of Birmingham.

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Abstract

Gamma oscillations, synchronous network activity between 30 and 100 Hz, have been linked to higher cognitive functions. Adenosine receptor modulation has been shown to alter cognitive function in animals and humans. In this thesis the effects of adenosine receptor modulation on in vitro and in vivo hippocampal gamma oscillations were investigated as well as the underlying mechanisms. \(A_1\)-receptor activation selectively decreased gamma oscillations while blocking \(A_1\)-receptors and activating \(A_{2A}\)-receptors increased gamma oscillations. Increasing endogenous adenosine levels suppressed gamma oscillations while decreasing endogenous adenosine levels facilitated gamma oscillations in vitro. Sharp electrode current clamp and whole-cell voltage clamp experiments showed that \(A_1\)-receptor activation hyperpolarised resting membrane potential, reduced firing rate and EPSP amplitude and shifted the IPSC reversal potential to more negative potentials. Blocking \(A_1\)-receptors increased pyramidal cell excitability and increased excitatory synaptic transmission. The results in vivo were more ambiguous but \(A_1\)-receptor activation decreased power in all frequency bands indicating that adenosine receptors can modulate hippocampal gamma oscillations in vivo. \(A_1\)-receptor blockage had no consistent effect on in vivo hippocampal gamma oscillations. Adenosine receptors modulate gamma oscillations in rodent hippocampal slices but are difficult targets for developing treatments that have cognitive benefits because of their ambiguous effects in vivo.

Type of Work:Ph.D. thesis.
Supervisor(s):Vreugdenhil, Martin and Jefferys, John G. R.
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:R Medicine (General)
QP Physiology
Institution:University of Birmingham
ID Code:1041
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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