Hippocampal Neural Disinhibition Causes Attentional and Memory Deficits
| Autor: | Tobias Bast, Robert Mason, Kevin C. F. Fone, Stephanie McGarrity, Marie A. Pezze |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Reflex Startle Cognitive Neuroscience Hippocampus Hippocampal formation 03 medical and health sciences Cellular and Molecular Neuroscience Bursting chemistry.chemical_compound 0302 clinical medicine medicine Animals Picrotoxin GABA-A Receptor Antagonists Cognitive decline Prepulse inhibition Neurons Memory Disorders Neural Inhibition medicine.disease Rats 030104 developmental biology chemistry nervous system Disinhibition Schizophrenia 5-choice-serial-reaction-time GABA inhibition hippocampus rat watermaze delayed-matching-to-place-test Attention Deficit Disorder with Hyperactivity medicine.symptom Psychology Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Cerebral cortex (New York, N.Y. : 1991). 27(9) |
| ISSN: | 1460-2199 1047-3211 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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