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dc.contributor.authorKlenowski, Paul M.
dc.contributor.authorZhao-Shea, Rubing
dc.contributor.authorFreels, Timothy G.
dc.contributor.authorMolas-Casacuberta, Susanna
dc.contributor.authorTapper, Andrew R.
dc.date2022-08-11T08:08:28.000
dc.date.accessioned2022-08-23T15:56:26Z
dc.date.available2022-08-23T15:56:26Z
dc.date.issued2022-02-01
dc.date.submitted2022-01-31
dc.identifier.citation<p>Klenowski PM, Zhao-Shea R, Freels TG, Molas S, Tapper AR. Dynamic activity of interpeduncular nucleus GABAergic neurons controls expression of nicotine withdrawal in male mice. Neuropsychopharmacology. 2022 Feb;47(3):641-651. doi: 10.1038/s41386-021-01107-1. Epub 2021 Jul 29. PMID: 34326477. <a href="https://doi.org/10.1038/s41386-021-01107-1">Link to article on publisher's site</a></p>
dc.identifier.issn0893-133X (Linking)
dc.identifier.doi10.1038/s41386-021-01107-1
dc.identifier.pmid34326477
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29967
dc.description.abstractA critical brain area implicated in nicotine dependence is the interpeduncular nucleus (IPN) located in the ventral midbrain and consisting primarily of GABAergic neurons. Previous studies indicate that IPN GABAergic neurons contribute to expression of somatic symptoms of nicotine withdrawal; however, whether IPN neurons are dynamically regulated during withdrawal in vivo and how this may contribute to both somatic and affective withdrawal behavior is unknown. To bridge this gap in knowledge, we expressed GCaMP in IPN GABAergic neurons and used in vivo fiber photometry to record changes in fluorescence, as a proxy for neuronal activity, in male mice during nicotine withdrawal. Mecamylamine-precipitated withdrawal significantly increased activity of IPN GABAergic neurons in nicotine-dependent, but not nicotine-naive mice. Analysis of GCaMP signals time-locked with somatic symptoms including grooming and scratching revealed reduced IPN GABAergic activity during these behaviors, specifically in mice undergoing withdrawal. In the elevated plus maze, used to measure anxiety-like behavior, an affective withdrawal symptom, IPN GABAergic neuron activity was increased during open-arm versus closed-arm exploration in nicotine-withdrawn, but not non-withdrawn mice. Optogenetic silencing IPN GABAergic neurons during withdrawal significantly reduced withdrawal-induced increases in somatic behavior and increased open-arm exploration. Together, our data indicate that IPN GABAergic neurons are dynamically regulated during nicotine withdrawal, leading to increased anxiety-like symptoms and somatic behavior, which inherently decrease IPN GABAergic neuron activity as a withdrawal-coping mechanism. These results provide a neuronal basis underlying the role of the IPN in the expression of somatic and affective behaviors of nicotine withdrawal.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=34326477&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1038/s41386-021-01107-1
dc.subjectNeuroscience and Neurobiology
dc.subjectPharmacology
dc.titleDynamic activity of interpeduncular nucleus GABAergic neurons controls expression of nicotine withdrawal in male mice
dc.typeJournal Article
dc.source.journaltitleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
dc.source.volume47
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/2169
dc.identifier.contextkey27891366
html.description.abstract<p>A critical brain area implicated in nicotine dependence is the interpeduncular nucleus (IPN) located in the ventral midbrain and consisting primarily of GABAergic neurons. Previous studies indicate that IPN GABAergic neurons contribute to expression of somatic symptoms of nicotine withdrawal; however, whether IPN neurons are dynamically regulated during withdrawal in vivo and how this may contribute to both somatic and affective withdrawal behavior is unknown. To bridge this gap in knowledge, we expressed GCaMP in IPN GABAergic neurons and used in vivo fiber photometry to record changes in fluorescence, as a proxy for neuronal activity, in male mice during nicotine withdrawal. Mecamylamine-precipitated withdrawal significantly increased activity of IPN GABAergic neurons in nicotine-dependent, but not nicotine-naive mice. Analysis of GCaMP signals time-locked with somatic symptoms including grooming and scratching revealed reduced IPN GABAergic activity during these behaviors, specifically in mice undergoing withdrawal. In the elevated plus maze, used to measure anxiety-like behavior, an affective withdrawal symptom, IPN GABAergic neuron activity was increased during open-arm versus closed-arm exploration in nicotine-withdrawn, but not non-withdrawn mice. Optogenetic silencing IPN GABAergic neurons during withdrawal significantly reduced withdrawal-induced increases in somatic behavior and increased open-arm exploration. Together, our data indicate that IPN GABAergic neurons are dynamically regulated during nicotine withdrawal, leading to increased anxiety-like symptoms and somatic behavior, which inherently decrease IPN GABAergic neuron activity as a withdrawal-coping mechanism. These results provide a neuronal basis underlying the role of the IPN in the expression of somatic and affective behaviors of nicotine withdrawal.</p>
dc.identifier.submissionpathfaculty_pubs/2169
dc.contributor.departmentTapper Lab
dc.contributor.departmentNeurobiology
dc.contributor.departmentBrudnick Neuropsychiatric Research Institute
dc.source.pages641-651


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