title: Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus.
abstract: 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.
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Jill
authors.initials: J
authors.lastname: Rocchetti
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Elsa
authors.initials: E
authors.lastname: Isingrini
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Gregory
authors.initials: G
authors.lastname: Dal Bo
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Sara
authors.initials: S
authors.lastname: Sagheby
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Aurore
authors.initials: A
authors.lastname: Menegaux
authors.affiliation: Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche en Santé 1130, and Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8246, Sorbonne University Université Pierre et Marie Curie, Neuroscience Paris Seine, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Tronche
authors.affiliation: Département de Pharmacie, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levesque
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Luc
authors.initials: L
authors.lastname: Moquin
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Gratton
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Tak Pan
authors.initials: TP
authors.lastname: Wong
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Instituto de Investigaciones en Ingenieria Genética y Biologia Molecular (CONICET), Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina. and Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Rubinstein
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada; Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche en Santé 1130, and Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8246, Sorbonne University Université Pierre et Marie Curie, Neuroscience Paris Seine, Paris, France. Electronic address: bruno.giros@mcgill.ca.
authors.forename: Bruno
authors.initials: B
authors.lastname: Giros
mesh_terms: D000818:Animals; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007858:Learning / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
chemical_list: C000600618:DRD2 protein, mouse; D065127:Dopamine D2 Receptor Antagonists; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2
keywords: Antipsychotics; D(2) dopamine receptors; LTD; Memory; Neuronal plasticity; Temporal hippocampus