The Role of Parvalbumin Interneuron GIRK Signaling in the Regulation of Affect and Cognition in Male and Female Mice
Pathological impairments in the regulation of affect (i.e., emotion) and flexible decision-making are commonly observed across numerous neuropsychiatric disorders and are thought to reflect dysfunction of cortical and subcortical circuits that arise in part from imbalances in excitation and inhibiti...
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Behavioral Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnbeh.2021.621751/full |
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| author | Eden M. Anderson Skyler Demis Hunter D’Acquisto Annabel Engelhardt Matthew Hearing |
| author_facet | Eden M. Anderson Skyler Demis Hunter D’Acquisto Annabel Engelhardt Matthew Hearing |
| author_sort | Eden M. Anderson |
| collection | DOAJ |
| description | Pathological impairments in the regulation of affect (i.e., emotion) and flexible decision-making are commonly observed across numerous neuropsychiatric disorders and are thought to reflect dysfunction of cortical and subcortical circuits that arise in part from imbalances in excitation and inhibition within these structures. Disruptions in GABA transmission, in particular, that from parvalbumin-expressing interneurons (PVI), has been highlighted as a likely mechanism by which this imbalance arises, as they regulate excitation and synchronization of principle output neurons. G protein-gated inwardly rectifying potassium ion (GIRK/Kir3) channels are known to modulate excitability and output of pyramidal neurons in areas like the medial prefrontal cortex and hippocampus; however, the role GIRK plays in PVI excitability and behavior is unknown. Male and female mice lacking GIRK1 in PVI (Girk1flox/flox:PVcre) and expressing td-tomato in PVI (Girk1flox/flox:PVCre:PVtdtom) exhibited increased open arm time in the elevated plus-maze, while males showed an increase in immobile episodes during the forced swim test (FST). Loss of GIRK1 did not alter motivated behavior for an appetitive reward or impair overall performance in an operant-based attention set-shifting model of cognitive flexibility; however it did alter types of errors committed during the visual cue test. Unexpectedly, baseline sex differences were also identified in these tasks, with females exhibiting overall poorer performance compared to males and distinct types of errors, highlighting potential differences in task-related problem-solving. Interestingly, reductions in PVI GIRK signaling did not correspond to changes in membrane excitability but did increase action potential (AP) firing at higher current injections in PVI of males, but not females. This is the first investigation on the role that PVI GIRK-signaling has on membrane excitability, AP firing, and their role on affect and cognition together increasing the understanding of PVI cellular mechanisms and function. |
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| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-12-13T19:00:28Z |
| publishDate | 2021-03-01 |
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| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-e86b1fcd34c74e8abcf3f21d416d89302022-12-21T23:34:43ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532021-03-011510.3389/fnbeh.2021.621751621751The Role of Parvalbumin Interneuron GIRK Signaling in the Regulation of Affect and Cognition in Male and Female MiceEden M. AndersonSkyler DemisHunter D’AcquistoAnnabel EngelhardtMatthew HearingPathological impairments in the regulation of affect (i.e., emotion) and flexible decision-making are commonly observed across numerous neuropsychiatric disorders and are thought to reflect dysfunction of cortical and subcortical circuits that arise in part from imbalances in excitation and inhibition within these structures. Disruptions in GABA transmission, in particular, that from parvalbumin-expressing interneurons (PVI), has been highlighted as a likely mechanism by which this imbalance arises, as they regulate excitation and synchronization of principle output neurons. G protein-gated inwardly rectifying potassium ion (GIRK/Kir3) channels are known to modulate excitability and output of pyramidal neurons in areas like the medial prefrontal cortex and hippocampus; however, the role GIRK plays in PVI excitability and behavior is unknown. Male and female mice lacking GIRK1 in PVI (Girk1flox/flox:PVcre) and expressing td-tomato in PVI (Girk1flox/flox:PVCre:PVtdtom) exhibited increased open arm time in the elevated plus-maze, while males showed an increase in immobile episodes during the forced swim test (FST). Loss of GIRK1 did not alter motivated behavior for an appetitive reward or impair overall performance in an operant-based attention set-shifting model of cognitive flexibility; however it did alter types of errors committed during the visual cue test. Unexpectedly, baseline sex differences were also identified in these tasks, with females exhibiting overall poorer performance compared to males and distinct types of errors, highlighting potential differences in task-related problem-solving. Interestingly, reductions in PVI GIRK signaling did not correspond to changes in membrane excitability but did increase action potential (AP) firing at higher current injections in PVI of males, but not females. This is the first investigation on the role that PVI GIRK-signaling has on membrane excitability, AP firing, and their role on affect and cognition together increasing the understanding of PVI cellular mechanisms and function.https://www.frontiersin.org/articles/10.3389/fnbeh.2021.621751/fullG protein-gated inwardly-rectifying K+GIRKparvalbuminprefrontal cortex cognitionaffect |
| spellingShingle | Eden M. Anderson Skyler Demis Hunter D’Acquisto Annabel Engelhardt Matthew Hearing The Role of Parvalbumin Interneuron GIRK Signaling in the Regulation of Affect and Cognition in Male and Female Mice Frontiers in Behavioral Neuroscience G protein-gated inwardly-rectifying K+ GIRK parvalbumin prefrontal cortex cognition affect |
| title | The Role of Parvalbumin Interneuron GIRK Signaling in the Regulation of Affect and Cognition in Male and Female Mice |
| title_full | The Role of Parvalbumin Interneuron GIRK Signaling in the Regulation of Affect and Cognition in Male and Female Mice |
| title_fullStr | The Role of Parvalbumin Interneuron GIRK Signaling in the Regulation of Affect and Cognition in Male and Female Mice |
| title_full_unstemmed | The Role of Parvalbumin Interneuron GIRK Signaling in the Regulation of Affect and Cognition in Male and Female Mice |
| title_short | The Role of Parvalbumin Interneuron GIRK Signaling in the Regulation of Affect and Cognition in Male and Female Mice |
| title_sort | role of parvalbumin interneuron girk signaling in the regulation of affect and cognition in male and female mice |
| topic | G protein-gated inwardly-rectifying K+ GIRK parvalbumin prefrontal cortex cognition affect |
| url | https://www.frontiersin.org/articles/10.3389/fnbeh.2021.621751/full |
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