cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use

Fyn kinase in the dorsomedial striatum (DMS) of rodents plays a central role in mechanisms underlying excessive alcohol intake. The DMS is comprised of medium spiny neurons (MSNs) that project directly (dMSNs) or indirectly (iMSNs) to the substantia nigra. Here, we examined the cell-type specificity...

Full description

Bibliographic Details
Authors: Ehinger, Yann, Morisot, Nadege, Phamluong, Khanhky, Sakhai, Samuel A., Soneja, Drishti, Adrover, Martín Federico, Alvarez, Veronica A., Ron, Dorit
Format: article
Status:Published version
Publication Date:2020
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/110263
Online Access:http://hdl.handle.net/11336/110263
Access Level:Open access
Keyword:FYN KINASE
CAMP SIGNALING
DORSOMEDIAL STRIATUM
ALCOHOL USE
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
id AR_95946b5dfdca061e71039d8c1a6fecb9
oai_identifier_str oai:ri.conicet.gov.ar:11336/110263
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use
title cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use
spellingShingle cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use
Ehinger, Yann
FYN KINASE
CAMP SIGNALING
DORSOMEDIAL STRIATUM
ALCOHOL USE
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
title_short cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use
title_full cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use
title_fullStr cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use
title_full_unstemmed cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use
title_sort cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use
dc.creator.none.fl_str_mv Ehinger, Yann
Morisot, Nadege
Phamluong, Khanhky
Sakhai, Samuel A.
Soneja, Drishti
Adrover, Martín Federico
Alvarez, Veronica A.
Ron, Dorit
author Ehinger, Yann
author_facet Ehinger, Yann
Morisot, Nadege
Phamluong, Khanhky
Sakhai, Samuel A.
Soneja, Drishti
Adrover, Martín Federico
Alvarez, Veronica A.
Ron, Dorit
author_role author
author2 Morisot, Nadege
Phamluong, Khanhky
Sakhai, Samuel A.
Soneja, Drishti
Adrover, Martín Federico
Alvarez, Veronica A.
Ron, Dorit
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv FYN KINASE
CAMP SIGNALING
DORSOMEDIAL STRIATUM
ALCOHOL USE
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
topic FYN KINASE
CAMP SIGNALING
DORSOMEDIAL STRIATUM
ALCOHOL USE
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
description Fyn kinase in the dorsomedial striatum (DMS) of rodents plays a central role in mechanisms underlying excessive alcohol intake. The DMS is comprised of medium spiny neurons (MSNs) that project directly (dMSNs) or indirectly (iMSNs) to the substantia nigra. Here, we examined the cell-type specificity of Fyn’s actions in alcohol use. First, we knocked down Fyn selectively in DMS dMSNs or iMSNs of mice and measured the level of alcohol consumption. We found that downregulation of Fyn in dMSNs, but not in iMSNs, reduces excessive alcohol but not saccharin intake. D1Rs are coupled to Gαs/olf, which activate cAMP signaling. To examine whether Fyn’s actions are mediated through cAMP signaling, DMS dMSNs were infected with GαsDREADD, and the activation of Fyn signaling was measured following CNO treatment. We found that remote stimulation of cAMP signaling in DMS dMSNs activates Fyn and promotes the phosphorylation of the Fyn substrate, GluN2B. In contract, remote activation of GαsDREADD in DLS dMSNs did not alter Fyn signaling. We then tested whether activation of GαsDREADD in DMS dMSNs or iMSNs alters alcohol intake and observed that CNO-dependent activation of GαsDREADD in DMS dMSNs but not iMSNs increases alcohol but not saccharin intake. Finally, we examined the contribution of Fyn to GαsDREADD-dependent increase in alcohol intake, and found that systemic administration of the Fyn inhibitor, AZD0503 blocks GαsDREADD-dependent increase in alcohol consumption. Our results suggest that the cAMP-Fyn axis in the DMS dMSNs is a molecular transducer of mechanisms underlying the development of excessive alcohol consumption.
publishDate 2020
dc.date.none.fl_str_mv 2020-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/110263
Ehinger, Yann; Morisot, Nadege; Phamluong, Khanhky; Sakhai, Samuel A.; Soneja, Drishti; et al.; cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use; Nature Publishing Group; Neuropsychopharmacology; 2020; 5-2020; 1-9
0893-133X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/110263
identifier_str_mv Ehinger, Yann; Morisot, Nadege; Phamluong, Khanhky; Sakhai, Samuel A.; Soneja, Drishti; et al.; cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use; Nature Publishing Group; Neuropsychopharmacology; 2020; 5-2020; 1-9
0893-133X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41386-020-0712-1
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41386-020-0712-1
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852539/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1799195604799193088
spelling cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol useEhinger, YannMorisot, NadegePhamluong, KhanhkySakhai, Samuel A.Soneja, DrishtiAdrover, Martín FedericoAlvarez, Veronica A.Ron, DoritFYN KINASECAMP SIGNALINGDORSOMEDIAL STRIATUMALCOHOL USEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Fyn kinase in the dorsomedial striatum (DMS) of rodents plays a central role in mechanisms underlying excessive alcohol intake. The DMS is comprised of medium spiny neurons (MSNs) that project directly (dMSNs) or indirectly (iMSNs) to the substantia nigra. Here, we examined the cell-type specificity of Fyn’s actions in alcohol use. First, we knocked down Fyn selectively in DMS dMSNs or iMSNs of mice and measured the level of alcohol consumption. We found that downregulation of Fyn in dMSNs, but not in iMSNs, reduces excessive alcohol but not saccharin intake. D1Rs are coupled to Gαs/olf, which activate cAMP signaling. To examine whether Fyn’s actions are mediated through cAMP signaling, DMS dMSNs were infected with GαsDREADD, and the activation of Fyn signaling was measured following CNO treatment. We found that remote stimulation of cAMP signaling in DMS dMSNs activates Fyn and promotes the phosphorylation of the Fyn substrate, GluN2B. In contract, remote activation of GαsDREADD in DLS dMSNs did not alter Fyn signaling. We then tested whether activation of GαsDREADD in DMS dMSNs or iMSNs alters alcohol intake and observed that CNO-dependent activation of GαsDREADD in DMS dMSNs but not iMSNs increases alcohol but not saccharin intake. Finally, we examined the contribution of Fyn to GαsDREADD-dependent increase in alcohol intake, and found that systemic administration of the Fyn inhibitor, AZD0503 blocks GαsDREADD-dependent increase in alcohol consumption. Our results suggest that the cAMP-Fyn axis in the DMS dMSNs is a molecular transducer of mechanisms underlying the development of excessive alcohol consumption.Fil: Ehinger, Yann. University of California San Francisco; Estados UnidosFil: Morisot, Nadege. University of California San Francisco; Estados Unidos. Nkarta Therapeutics; Estados UnidosFil: Phamluong, Khanhky. University of California San Francisco; Estados UnidosFil: Sakhai, Samuel A.. University of California San Francisco; Estados Unidos. Sage Therapeutics; Estados UnidosFil: Soneja, Drishti. University of California San Francisco; Estados UnidosFil: Adrover, Martín Federico. University Of California San Francisco (ucsf); Estados Unidos. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Alvarez, Veronica A.. National Institutes of Health; Estados UnidosFil: Ron, Dorit. University of California San Francisco; Estados UnidosNature Publishing Group2020-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/110263Ehinger, Yann; Morisot, Nadege; Phamluong, Khanhky; Sakhai, Samuel A.; Soneja, Drishti; et al.; cAMP-Fyn signaling in the dorsomedial striatum direct pathway drives excessive alcohol use; Nature Publishing Group; Neuropsychopharmacology; 2020; 5-2020; 1-90893-133XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41386-020-0712-1info:eu-repo/semantics/altIdentifier/doi/10.1038/s41386-020-0712-1info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852539/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:57:48Zoai:ri.conicet.gov.ar:11336/110263instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 13:57:48.616CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
score 15,812455

Similar Items