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J Psychopharmacol. 2006 May;20(3):356-72. Epub 2005 Sep 20.

Dysregulation of thalamic sensory "transmission" in schizophrenia: neurochemical vulnerability to hallucinations.

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  • 1The Retreat Hospital, Heslington Road, York, UK.


Cholinergic arousal mechanisms predispose thalamic and cortical neurons to fire action potentials at gamma rhythms, which have a tendency to resonate in thalamocortical networks, thereby forming coherent assemblies under constraints of sensory input to specific thalamic nuclei, on the one hand, and prefrontal and limbic attentional mechanisms, on the other. Perception may be based on sustained assemblies of coherent gamma oscillations in thalamocortical circuits. In schizophrenia, the impact of sensory input on self-organization of thalamocortical activity may be generally reduced. As a result, processes underlying perception can become uncoupled from sensory input, particularly at times of hyperarousal, leading to domination of attentional mechanisms and the emergence of hallucinations. Evidence is reviewed that implicates excessive neuronal noise in specific thalamic nuclei in the generation of hallucinations in schizophrenia. Nicotinic receptor abnormalities, dopaminergic hyperactivity and glutamate-receptor hypofunction are reconciled within a model of psychotic symptom generation that places crucial emphasis on dysfunction of the reticular thalamic nucleus.

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