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

  • Jill Rocchetti
    Affiliations
    Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
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  • Elsa Isingrini
    Affiliations
    Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
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  • Gregory Dal Bo
    Affiliations
    Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
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  • Sara Sagheby
    Affiliations
    Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
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  • Aurore Menegaux
    Affiliations
    Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
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  • François Tronche
    Affiliations
    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
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  • Daniel Levesque
    Affiliations
    Département de Pharmacie, Université de Montréal, Montreal, Quebec, Canada
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  • Luc Moquin
    Affiliations
    Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
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  • Alain Gratton
    Affiliations
    Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
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  • Tak Pan Wong
    Affiliations
    Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
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  • Marcelo Rubinstein
    Affiliations
    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
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  • Bruno Giros
    Correspondence
    Address correspondence to Bruno Giros, Ph.D., Department of Psychiatry, Douglas Mental Health University Institute, 6875 Lasalle Boulevard, McGill University, Montreal, Quebec, H4H 1R3, Canada
    Affiliations
    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
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      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.

      Keywords

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