Dopamine Regulates Aversive Contextual Learning and Associated In Vivo Synaptic Plasticity in the Hippocampus

Cell Rep. 2016 Mar 1;14(8):1930-9. doi: 10.1016/j.celrep.2016.01.070. Epub 2016 Feb 18.

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.

Keywords: LTP; fear conditioning; inhibitory avoidance; in vivo recording; memory; passive avoidance; ventral tegmental area.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology*
  • Benzazepines / pharmacology
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / physiology*
  • CA3 Region, Hippocampal / cytology
  • CA3 Region, Hippocampal / drug effects
  • CA3 Region, Hippocampal / physiology
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology
  • Dopamine / metabolism*
  • Electrodes
  • Learning / physiology*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Memory, Long-Term / drug effects
  • Memory, Long-Term / physiology*
  • Mesencephalon / cytology
  • Mesencephalon / drug effects
  • Mesencephalon / physiology
  • Mice
  • Mice, Inbred C57BL
  • Microtomy
  • Pyramidal Cells / cytology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • Receptors, Dopamine D1 / agonists
  • Receptors, Dopamine D1 / physiology
  • Synapses / drug effects
  • Synapses / physiology
  • Synapses / ultrastructure
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Tissue Culture Techniques

Substances

  • Benzazepines
  • Receptors, Dopamine D1
  • SCH 23390
  • Dopamine