Dysregulation of thalamic sensory "transmission" in schizophrenia: neurochemical vulnerability to hallucinations.
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.
Behrendt
Ralf-Peter
RP
The Retreat Hospital, Heslington Road, York, UK. rp.behrendt@btinternet.com
D000109:Acetylcholine / Q000378:metabolism; D001143:Arousal / Q000502:physiology; D001288:Attention / Q000502:physiology; D002540:Cerebral Cortex / Q000503:physiopathology; D006212:Hallucinations / Q000503:physiopathology; D006801:Humans; D020646:Intralaminar Thalamic Nuclei / Q000503:physiopathology; D009415:Nerve Net / Q000503:physiopathology; D011954:Receptors, Dopamine / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D011978:Receptors, Nicotinic / Q000502:physiology; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*; D011984:Sensory Receptor Cells / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications; D009435:Synaptic Transmission / Q000502:physiology*; D013788:Thalamus / Q000503:physiopathology*
D011954:Receptors, Dopamine; D017470:Receptors, Glutamate; D011978:Receptors, Nicotinic; D000109:Acetylcholine