Cortical inhibitory neurons and schizophrenia.
Impairments in certain cognitive functions, such as working memory, are core features of schizophrenia. Convergent findings indicate that a deficiency in signalling through the TrkB neurotrophin receptor leads to reduced GABA (gamma-aminobutyric acid) synthesis in the parvalbumin-containing subpopulation of inhibitory GABA neurons in the dorsolateral prefrontal cortex of individuals with schizophrenia. Despite both pre- and postsynaptic compensatory responses, the resulting alteration in perisomatic inhibition of pyramidal neurons contributes to a diminished capacity for the gamma-frequency synchronized neuronal activity that is required for working memory function. These findings reveal specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.
Lewis
David A
DA
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. lewisda@upmc.edu
Hashimoto
Takanori
T
Volk
David W
DW
D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology* / Q000503:physiopathology*; D006801:Humans; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D012559:Schizophrenia / Q000473:pathology / Q000503:physiopathology*