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...

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Published inBiological psychiatry (1969) Vol. 77; no. 6; pp. 513 - 525
Main Authors Rocchetti, 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
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LanguageEnglish
Published United States Elsevier Inc 15.03.2015
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Abstract 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.
AbstractList BACKGROUNDDysfunctional 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.METHODSFollowing 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.RESULTSDopamine 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.CONCLUSIONSPresynaptic 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.
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. 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. 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. 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.
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.
Author Giros, Bruno
Dal Bo, Gregory
Levesque, Daniel
Rubinstein, Marcelo
Moquin, Luc
Rocchetti, Jill
Menegaux, Aurore
Tronche, François
Gratton, Alain
Sagheby, Sara
Isingrini, Elsa
Wong, Tak Pan
Author_xml – sequence: 1
  fullname: Rocchetti, Jill
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  fullname: Dal Bo, Gregory
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  fullname: Menegaux, Aurore
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  fullname: Tronche, François
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  fullname: Levesque, Daniel
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  fullname: Moquin, Luc
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  fullname: Gratton, Alain
– sequence: 10
  fullname: Wong, Tak Pan
– sequence: 11
  fullname: Rubinstein, Marcelo
– sequence: 12
  fullname: Giros, Bruno
BackLink https://www.ncbi.nlm.nih.gov/pubmed/24742619$$D View this record in MEDLINE/PubMed
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Issue 6
Keywords Antipsychotics
D 2 dopamine receptors
Neuronal plasticity
Temporal hippocampus
LTD
Memory
D2 dopamine receptors
D dopamine receptors
Language English
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Snippet Abstract Background Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with...
Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders....
BACKGROUNDDysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric...
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SubjectTerms Animals
Antipsychotics
D2 dopamine receptors
Dopamine D2 Receptor Antagonists - pharmacology
Excitatory Postsynaptic Potentials - drug effects
Excitatory Postsynaptic Potentials - physiology
Hippocampus - drug effects
Hippocampus - physiology
Learning - drug effects
Learning - physiology
Long-Term Potentiation - drug effects
Long-Term Potentiation - physiology
Long-Term Synaptic Depression - drug effects
Long-Term Synaptic Depression - physiology
LTD
Male
Memory
Memory - drug effects
Memory - physiology
Mice, Inbred C57BL
Mice, Transgenic
Neural Pathways - drug effects
Neural Pathways - physiology
Neuronal plasticity
Psychiatry
Receptors, Dopamine D2 - genetics
Receptors, Dopamine D2 - metabolism
RNA, Messenger - metabolism
Space Perception - drug effects
Space Perception - physiology
Temporal hippocampus
Ventral Tegmental Area - drug effects
Ventral Tegmental Area - physiology
Title Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus
URI https://www.clinicalkey.es/playcontent/1-s2.0-S0006322314001668
https://dx.doi.org/10.1016/j.biopsych.2014.03.013
https://www.ncbi.nlm.nih.gov/pubmed/24742619
https://search.proquest.com/docview/1656043528
Volume 77
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