β-Adrenergic signaling is required for the induction of a labile state during memory reconsolidation

Brain Res Bull. 2018 Jul:141:50-57. doi: 10.1016/j.brainresbull.2018.04.011. Epub 2018 Apr 20.

Abstract

Memory reconsolidation is the process by which previously consolidated memories reenter a labile state through reactivation of the memory trace and are actively consolidated through de novo protein synthesis. Although extensive studies have shown that β-adrenergic signaling plays a critical role in the restabilization of reactivated memory, its role in the destabilization of long-term memory is not well-studied. In this study, we found that membrane excitability increased in hippocampal CA1 neurons immediately after the retrieval of contextual fear memory. Interestingly, this increase in membrane excitability diminished after treatment with propranolol (a β-adrenergic receptor antagonist), an NMDA receptor antagonist, and a PKA inhibitor. In addition, we found that administration of propranolol prior to, but not after, the retrieval of fear memory ameliorated the memory impairment caused by anisomycin, indicating that inhibition of β-adrenergic signaling blocks the destabilization of contextual fear memory. Taken together, these results indicate that β-adrenergic signaling via NMDA receptors and PKA signaling pathway induces a labile state of long-term memory through increased neuronal membrane excitability.

Keywords: Long-term memory; Membrane excitability; Propranolol; Reconsolidation; β-adrenergic signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / physiology*
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Fear / drug effects
  • Fear / physiology
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology*
  • Memory Consolidation / drug effects
  • Memory Consolidation / physiology*
  • Mental Recall / drug effects
  • Mental Recall / physiology
  • Mice, Inbred C57BL
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurotransmitter Agents / pharmacology
  • Propranolol / pharmacology
  • Receptors, Adrenergic, beta / metabolism*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Signal Transduction / drug effects
  • Tissue Culture Techniques

Substances

  • Neurotransmitter Agents
  • Receptors, Adrenergic, beta
  • Receptors, N-Methyl-D-Aspartate
  • Propranolol
  • Cyclic AMP-Dependent Protein Kinases