Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition

被引：76

作者：

Bast, Tobias ^{[1
]}

Pezze, Marie ^{[1
]}

McGarrity, Stephanie ^{[1
]}

机构：

[1] Univ Nottingham, Sch Psychol & Neurosci Nottingham, Nottingham, England

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 2017年 / 174卷 / 19期

基金：

英国生物技术与生命科学研究理事会;

关键词：

POSITIVE ALLOSTERIC MODULATORS; GAMMA-AMINOBUTYRIC-ACID; VENTRAL HIPPOCAMPUS; MOUSE MODEL; ATTENTIONAL PERFORMANCE; GABA(A) RECEPTORS; NUCLEUS-ACCUMBENS; AGED RATS; GABAERGIC INTERNEURONS; TREATMENT STRATEGIES;

D O I：

10.1111/bph.13850

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition contributes to clinically relevant cognitive deficits, and we consider pharmacological strategies for ameliorating cognitive deficits by rebalancing disinhibition-induced aberrant neural activity.

引用

页码：3211 / 3225

页数：15

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