Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition
We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, i.e. deficient GABA transmission, within prefrontal cortex and hippocampus for clinically relevant cognitive functions. Both regions support important cognitive functions, including att...
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| Format: | Article |
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Wiley
2017
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| Online Access: | https://eprints.nottingham.ac.uk/42647/ |
| _version_ | 1848796536500125696 |
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| author | Bast, Tobias Pezze, Marie McGarrity, Stephanie |
| author_facet | Bast, Tobias Pezze, Marie McGarrity, Stephanie |
| author_sort | Bast, Tobias |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, i.e. deficient GABA transmission, within prefrontal cortex and 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 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. |
| first_indexed | 2025-11-14T19:49:33Z |
| format | Article |
| id | nottingham-42647 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:49:33Z |
| publishDate | 2017 |
| publisher | Wiley |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-426472020-05-04T19:55:06Z https://eprints.nottingham.ac.uk/42647/ Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition Bast, Tobias Pezze, Marie McGarrity, Stephanie We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, i.e. deficient GABA transmission, within prefrontal cortex and 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 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. Wiley 2017-10 Article PeerReviewed Bast, Tobias, Pezze, Marie and McGarrity, Stephanie (2017) Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition. British Journal of Pharmacology, 174 (19). pp. 3211-3225. ISSN 1476-5381 http://onlinelibrary.wiley.com/doi/10.1111/bph.13850/full doi:10.1111/bph.13850 doi:10.1111/bph.13850 |
| spellingShingle | Bast, Tobias Pezze, Marie McGarrity, Stephanie Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition |
| title | Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition |
| title_full | Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition |
| title_fullStr | Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition |
| title_full_unstemmed | Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition |
| title_short | Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition |
| title_sort | cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition |
| url | https://eprints.nottingham.ac.uk/42647/ https://eprints.nottingham.ac.uk/42647/ https://eprints.nottingham.ac.uk/42647/ |