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The effect of ketamine on visual perception and its relation to γ oscillations in rat visual cortex.

Ward, Katja (2011)
M.Res. thesis, University of Birmingham.

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Pathological psychosis is little understood, but has been related to impaired function of parvalbumin expressing interneurons, which in the normal brain drive the synchronisation of cortical activity in the gamma frequency band (γ 30-120 Hz). Pharmacologically-induced NMDA receptor hypofunction mimics the state of distorted perception and hallucinations, possibly by the same mechanism that underlies the pathology. High-frequency (65-120 Hz) and low frequency (30-65 Hz) γ coexist in the visual cortex in vivo, and are in vitro generated by independent networks in the superficial layer and deep layers respectively. The psychotomimetic NMDA receptor antagonist ketamine causes a selective deceleration of high-frequency-γ in vitro, which results in phase-locking of the two oscillators; which was proposed as a mechanism of hallucinogenesis.
We wanted to test whether the ketamine-induced distortion of visual perception was related to the phase-locking of γ in layer III and γ in layer V of the visual cortex. A visual discrimination task with image pairs of different signal/noise levels was designed for a touch-screen operant chamber, to assess visual perception in the rat, while recording local field potentials from electrodes implanted in layer III and V of the visual cortex.
In the first 30 minutes post-injection, ketamine (2 or 4 mg/kg sc) dose-dependently shifted the relationship between % correct and % signal in the direction of impaired perception, without affecting the ability to select the correct 100% signal images.
Ketamine dose-dependently increased the power of the γ oscillation in both layers, but without affecting the high frequency-γ / low-frequency-γ power ratio. In contrast to in vitro recordings, there was no indication of a layer specific distribution of high- and low-frequency-γ in either layer, and in the absence of distinct oscillators phase locking could not be assessed.
The relation between ketamine-induced effect on γ-power and effect on perception suggests an optimum ketamine dose at which γ-oscillations are sufficiently increased to improve perception, whereas higher doses cause impairment of perception probably by hypersynchronisation. It is considered that this model can be used to assess antipsychotic treatments and to improve neuroleptic drugs in the future.

Type of Work:M.Res. thesis.
Supervisor(s):Vreugdenhil, Martin
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:RB Pathology
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
RE Ophthalmology
Institution:University of Birmingham
ID Code:3228
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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