Molecular, Circuit, and Stress Response Characterization of Ventral Pallidum Npas1-Neurons

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dc.contributor.authorMorais-Silva, Gessynger [UNESP]
dc.contributor.authorCampbell, Rianne R.
dc.contributor.authorNam, Hyungwoo
dc.contributor.authorBasu, Mahashweta
dc.contributor.authorPagliusi, Marco
dc.contributor.authorFox, Megan E.
dc.contributor.authorChan, C. Savio
dc.contributor.authorIñiguez, Sergio D.
dc.contributor.authorAment, Seth
dc.contributor.authorCramer, Nathan
dc.contributor.authorMarin, Marcelo Tadeu [UNESP]
dc.contributor.authorLobo, Mary Kay
dc.contributor.institutionSchool of Medicine
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionNorthwestern University
dc.contributor.institutionUniversity of Texas at El Paso
dc.date.accessioned2023-07-29T13:38:03Z
dc.date.available2023-07-29T13:38:03Z
dc.date.issued2023-01-18
dc.description.abstractAltered activity of the ventral pallidum (VP) underlies disrupted motivation in stress and drug exposure. The VP is a very heterogeneous structure composed of many neuron types with distinct physiological properties and projections. Neuronal PAS 1-positive (Npas11) VP neurons are thought to send projections to brain regions critical for motivational behavior. While Npas11 neurons have been characterized in the globus pallidus external, there is limited information on these neurons in the VP. To address this limitation, we evaluated the projection targets of the VP Npas11 neurons and performed RNA-sequencing on ribosome-associated mRNA from VP Npas11 neurons to determine their molecular identity. Finally, we used a chemogenetic approach to manipulate VP Npas11 neurons during social defeat stress (SDS) and behavioral tasks related to anxiety and motivation in Npas1-Cre mice. We used a similar approach in females using the chronic witness defeat stress (CWDS). We identified VP Npas11 projections to the nucleus accumbens, ventral tegmental area, medial and lateral habenula, lateral hypothalamus, thalamus, medial and lateral septum, and periaqueductal gray area. VP Npas11 neurons displayed distinct translatome representing distinct biological processes. Chemogenetic activation of hM3D(Gq) receptors in VP Npas11 neurons increased susceptibility to a subthreshold SDS and anxiety-like behavior in the elevated plus maze and open field while the activation of hM4D(Gi) receptors in VP Npas11 neurons enhanced resilience to chronic SDS and CWDS. Thus, the activity of VP Npas11 neurons modulates susceptibility to social stressors and anxiety-like behavior. Our studies provide new information on VP Npas11 neuron circuitry, molecular identity, and their role in stress response.en
dc.description.affiliationDepartment of Anatomy and Neurobiology University of Maryland School of Medicine
dc.description.affiliationSao Paulo State University (UNESP) School of Pharmaceutical Sciences Laboratory of Pharmacology, Araraquara
dc.description.affiliationJoint Graduate Program in Physiological Sciences Federal University of São Carlos Sao Paulo State University, Araraquara
dc.description.affiliationDepartment of Psychiatry University of Maryland School of Medicine
dc.description.affiliationInstitute for Genome Sciences University of Maryland School of Medicine
dc.description.affiliationDepartment of Structural and Functional Biology State University of Campinas
dc.description.affiliationDepartment of Neuroscience Feinberg School of Medicine Northwestern University
dc.description.affiliationDepartment of Psychology University of Texas at El Paso
dc.description.affiliationUnespSao Paulo State University (UNESP) School of Pharmaceutical Sciences Laboratory of Pharmacology, Araraquara
dc.description.affiliationUnespJoint Graduate Program in Physiological Sciences Federal University of São Carlos Sao Paulo State University, Araraquara
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipIdNational Institutes of Health: R01-DA-038613
dc.description.sponsorshipIdNational Institutes of Health: R01-DA-047843
dc.description.sponsorshipIdNational Institutes of Health: R01-MH-106500
dc.format.extent405-418
dc.identifierhttp://dx.doi.org/10.1523/JNEUROSCI.0971-22.2022
dc.identifier.citationJournal of Neuroscience, v. 43, n. 3, p. 405-418, 2023.
dc.identifier.doi10.1523/JNEUROSCI.0971-22.2022
dc.identifier.issn1529-2401
dc.identifier.issn0270-6474
dc.identifier.scopus2-s2.0-85146532116
dc.identifier.urihttp://hdl.handle.net/11449/248226
dc.language.isoeng
dc.relation.ispartofJournal of Neuroscience
dc.sourceScopus
dc.subjectdepression
dc.subjectDREAADs
dc.subjectNpas1
dc.subjectsocial defeat stress
dc.subjectventral pallidum
dc.titleMolecular, Circuit, and Stress Response Characterization of Ventral Pallidum Npas1-Neuronsen
dc.typeArtigo

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