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Hippocampal neural disinhibition causes attentional and memory deficits

McGarrity, Stephanie; Mason, Rob; Fone, Kevin C.F.; Pezze, Marie A.; Bast, Tobias

Authors

Stephanie McGarrity

Rob Mason

Kevin C.F. Fone kevin.fone@nottingham.ac.uk

Marie A. Pezze

Tobias Bast



Abstract

Subconvulsive hippocampal neural disinhibition, that is reduced GABAergic inhibition, has been implicated in neuropsychiatric disorders characterized by attentional and memory deficits, including schizophrenia and age-related cognitive decline. Considering that neural disinhibition may disrupt both intra-hippocampal processing and processing in hippocampal projection sites, we hypothesized that hippocampal disinhibition disrupts hippocampus-dependent memory performance and, based on strong hippocampo-prefrontal connectivity, also prefrontal-dependent attention. In support of this hypothesis, we report that acute hippocampal disinhibition by microinfusion of the GABA-A receptor antagonist picrotoxin in rats impaired hippocampus-dependent everyday-type rapid place learning performance on the watermaze delayed-matching-to-place test and prefrontal-dependent attentional performance on the 5-choice-serial-reaction-time test, which does not normally require the hippocampus. For comparison, we also examined psychosis-related sensorimotor effects, using startle/prepulse inhibition (PPI) and locomotor testing. Hippocampal picrotoxin moderately increased locomotion and slightly reduced startle reactivity, without affecting PPI. In vivo electrophysiological recordings in the vicinity of the infusion site showed that picrotoxin mainly enhanced burst firing of hippocampal neurons. In conclusion, hippocampal neural disinhibition disrupts hippocampus-dependent memory performance and also manifests through deficits in not normally hippocampus-dependent attentional performance. These behavioral deficits may reflect a disrupted control of burst firing, which may disrupt hippocampal processing and cause aberrant drive to hippocampal projection sites.

Journal Article Type Article
Publication Date Sep 1, 2017
Journal Cerebral Cortex
Print ISSN 1047-3211
Electronic ISSN 1460-2199
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 27
Issue 9
APA6 Citation McGarrity, S., Mason, R., Fone, K. C., Pezze, M. A., & Bast, T. (2017). Hippocampal neural disinhibition causes attentional and memory deficits. Cerebral Cortex, 27(9), doi:10.1093/cercor/bhw247
DOI https://doi.org/10.1093/cercor/bhw247
Keywords 5-choice-serial-reaction-time, GABA inhibition, hippocampus, rat, watermaze delayed-matching-to-place-test
Publisher URL http://cercor.oxfordjournals.org/content/early/2016/08/22/cercor.bhw247
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
Additional Information This is a pre-copyedited, author-produced version of an article accepted for publication in Cerebral cortex following peer review. The version of record Hippocampal Neural Disinhibition Causes Attentional and Memory Deficits / Stephanie McGarrity, Rob Mason, Kevin C. Fone, Marie Pezze1, and Tobias Bast is available online at: https://academic.oup.co...al-Disinhibition-Causes

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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