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Title: In vitro and in vivo electrophysiological investigations into the role of nicotinic receptors in the rat hippocampus
Author: Bratley , Claire Tamsyn
ISNI:       0000 0004 5920 6708
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2014
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Nicotinic cholinergic receptors within the hippocampus are hypothesised to modulate memory: nicotinic agonists can enhance hippocampal dependent memory. Moreover, nicotine is an addictive drug whose removal produces an extended withdrawal state. Extracellular electro physiological recordings were conducted in vitro to assess nicotinic actions upon synaptic transmission and intrinsic neuronal excitability in subfield CAl of the hippocampus. Agonists (PNU-282987 and SSR180711) and a positive allosteric modulator (PNU-120596) of the alpha7 nicotinic receptor were bath applied. PNU- 120596 in presence of nicotine caused a sustained depression of CAl synaptic responses. Recordings of local field potentials (includ ing theta and gamma oscillations) and action potential firing were made from the hippocampus of awake freely moving rats. An acute dose of SSR180711 was without effect. Effects were then sought of chronically administered nicotine and its withdrawal. Chronic nicotine administration enhanced performance of an object location (Ol) recognition memory task in which a rat spontaneously explores an object in a novel and a familiar location. Hippocampal theta-gamma phase amplitude coupling (PAC) was greater during exploration of an object in the familiar than in the novel location. However, PAC changes did not parallel nicotine's effect on performance of the Ol task. During the Ol task, PAC in CAl and the dentate gyrus was enhanced following nicotine administration but did not return to baseline following withdrawal. Nicotine withdrawal was associated with an increase in the firing rate of CAl and CA3 neurones. Nicotine enhanced theta-gamma phase amplitude coupling (PAC) in CAl, whereas in CA3 it decreased PAC when the animal was mobile but under no cognitive load. PAC, theta and gamma power were lower in CAl than in CA3; they were highest in the dentate gyrus. In sum, nicotine administration was found to enhance object location memory and produce long lasting changes to hippocampal oscillations and theta-gamma coupling.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available