title: Dopamine Regulates Aversive Contextual Learning and Associated In Vivo Synaptic Plasticity in the Hippocampus.
abstract: Dopamine release during reward-driven behaviors influences synaptic plasticity. However, dopamine innervation and release in the hippocampus and its role during aversive behaviors are controversial. Here, we show that in vivo hippocampal synaptic plasticity in the CA3-CA1 circuit underlies contextual learning during inhibitory avoidance (IA) training. Immunohistochemistry and molecular techniques verified sparse dopaminergic innervation of the hippocampus from the midbrain. The long-term synaptic potentiation (LTP) underlying the learning of IA was assessed with a D1-like dopamine receptor agonist or antagonist in ex vivo hippocampal slices and in vivo in freely moving mice. Inhibition of D1-like dopamine receptors impaired memory of the IA task and prevented the training-induced enhancement of both ex vivo and in vivo LTP induction. The results indicate that dopamine-receptor signaling during an aversive contextual task regulates aversive memory retention and regulates associated synaptic mechanisms in the hippocampus that likely underlie learning.
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: John I
authors.initials: JI
authors.lastname: Broussard
authors.affiliation: Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, Philadelphia, PA 19104, USA.
authors.forename: Kechun
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Amber T
authors.initials: AT
authors.lastname: Levine
authors.affiliation: Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, Philadelphia, PA 19104, USA.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Tsetsenis
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jenson
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Cao
authors.affiliation: Program in Developmental Biology , Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Isabella
authors.initials: I
authors.lastname: Garcia
authors.affiliation: Program in Developmental Biology , Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Arenkiel
authors.affiliation: Department of Pharmacology, University of Tennessee, Memphis, TN 38163 USA.
authors.forename: Fu-Ming
authors.initials: FM
authors.lastname: Zhou
authors.affiliation: Department of Psychiatry, Mahoney Institute for Neurosciences, Perelman School for Medicine, Philadelphia, PA 19104, USA.
authors.forename: Mariella
authors.initials: M
authors.lastname: De Biasi
authors.affiliation: Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, Philadelphia, PA 19104, USA. Electronic address: johndani@upenn.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Dani
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001552:Benzazepines / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004566:Electrodes; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology*; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008867:Microtomy; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D001552:Benzazepines; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D004298:Dopamine
keywords: LTP; fear conditioning; inhibitory avoidance; in vivo recording; memory; passive avoidance; ventral tegmental area