Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus

Autores
Rocchett, Jill; Isingrini, Elsa; Dal Bo, Gregory; Sagheby, Sara; Menegaux, Aurore; Tronche, François; Levesque, Daniel; Moquin, Luc; Gratton, Alain; Wong, Tak Pan; Rubinstein, Marcelo; Giros, Bruno
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND: Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. METHODS: Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naïve mice (n = 4-21) were used in the different procedures. RESULTS: Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. CONCLUSIONS: Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders.
Fil: Rocchett, Jill. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Isingrini, Elsa. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Dal Bo, Gregory. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Sagheby, Sara. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Menegaux, Aurore. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Tronche, François. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Levesque, Daniel. Université de Montréal. Département de Pharmacie; Canadá
Fil: Moquin, Luc. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Gratton, Alain. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Wong, Tak Pan. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
Fil: Giros, Bruno. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Materia
Dopamina
Receptor D2
Ratones Transgénicos
Hipocampo
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/3946
Acceder
id CONICETDig_98f16c426e0027b6c6f08b26a318f5cc
oai_identifier_str oai:ri.conicet.gov.ar:11336/3946
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal HippocampusRocchett, JillIsingrini, ElsaDal Bo, GregorySagheby, SaraMenegaux, AuroreTronche, FrançoisLevesque, DanielMoquin, LucGratton, AlainWong, Tak PanRubinstein, MarceloGiros, BrunoDopaminaReceptor D2Ratones TransgénicosHipocampohttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3BACKGROUND: Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. METHODS: Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naïve mice (n = 4-21) were used in the different procedures. RESULTS: Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. CONCLUSIONS: Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders.Fil: Rocchett, Jill. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; CanadáFil: Isingrini, Elsa. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; CanadáFil: Dal Bo, Gregory. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; CanadáFil: Sagheby, Sara. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; CanadáFil: Menegaux, Aurore. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; CanadáFil: Tronche, François. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Levesque, Daniel. Université de Montréal. Département de Pharmacie; CanadáFil: Moquin, Luc. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; CanadáFil: Gratton, Alain. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; CanadáFil: Wong, Tak Pan. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; CanadáFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Giros, Bruno. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; FranciaElsevier2015-03-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/3946Rocchett, Jill; Isingrini, Elsa; Dal Bo, Gregory; Sagheby, Sara; Menegaux, Aurore; et al.; Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus; Elsevier; Biological Psychiatry; 77; 6; 15-3-2015; 513-5250006-3223enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0006322314001668info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biopsych.2014.03.013info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:05:02Zoai:ri.conicet.gov.ar:11336/3946instacron: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:34982025-09-10 13:05:03.162CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus
title Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus
spellingShingle Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus
Rocchett, Jill
Dopamina
Receptor D2
Ratones Transgénicos
Hipocampo
title_short Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus
title_full Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus
title_fullStr Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus
title_full_unstemmed Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus
title_sort Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus
dc.creator.none.fl_str_mv Rocchett, Jill
Isingrini, Elsa
Dal Bo, Gregory
Sagheby, Sara
Menegaux, Aurore
Tronche, François
Levesque, Daniel
Moquin, Luc
Gratton, Alain
Wong, Tak Pan
Rubinstein, Marcelo
Giros, Bruno
author Rocchett, Jill
author_facet Rocchett, Jill
Isingrini, Elsa
Dal Bo, Gregory
Sagheby, Sara
Menegaux, Aurore
Tronche, François
Levesque, Daniel
Moquin, Luc
Gratton, Alain
Wong, Tak Pan
Rubinstein, Marcelo
Giros, Bruno
author_role author
author2 Isingrini, Elsa
Dal Bo, Gregory
Sagheby, Sara
Menegaux, Aurore
Tronche, François
Levesque, Daniel
Moquin, Luc
Gratton, Alain
Wong, Tak Pan
Rubinstein, Marcelo
Giros, Bruno
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Dopamina
Receptor D2
Ratones Transgénicos
Hipocampo
topic Dopamina
Receptor D2
Ratones Transgénicos
Hipocampo
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv BACKGROUND: Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. METHODS: Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naïve mice (n = 4-21) were used in the different procedures. RESULTS: Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. CONCLUSIONS: Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders.
Fil: Rocchett, Jill. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Isingrini, Elsa. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Dal Bo, Gregory. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Sagheby, Sara. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Menegaux, Aurore. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Tronche, François. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Levesque, Daniel. Université de Montréal. Département de Pharmacie; Canadá
Fil: Moquin, Luc. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Gratton, Alain. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Wong, Tak Pan. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
Fil: Giros, Bruno. McGill University. Douglas Mental Health University Institute. Department of Psychiatry; Canadá. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
description BACKGROUND: Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. METHODS: Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naïve mice (n = 4-21) were used in the different procedures. RESULTS: Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. CONCLUSIONS: Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders.
publishDate 2015
dc.date.none.fl_str_mv 2015-03-15
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/11336/3946
Rocchett, Jill; Isingrini, Elsa; Dal Bo, Gregory; Sagheby, Sara; Menegaux, Aurore; et al.; Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus; Elsevier; Biological Psychiatry; 77; 6; 15-3-2015; 513-525
0006-3223
url http://hdl.handle.net/11336/3946
identifier_str_mv Rocchett, Jill; Isingrini, Elsa; Dal Bo, Gregory; Sagheby, Sara; Menegaux, Aurore; et al.; Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus; Elsevier; Biological Psychiatry; 77; 6; 15-3-2015; 513-525
0006-3223
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0006322314001668
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biopsych.2014.03.013
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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
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score 12.993085

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