Ward, Katja (2011)
M.Res. thesis, University of Birmingham.
Restricted to Repository staff only until 01 January 2032.
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.
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