Astrocytic β2-adrenergic Receptors Mediate Hippocampal Long-Term Memory Consolidation

Proc Natl Acad Sci U S A. 2016 Jul 26;113(30):8526-31. doi: 10.1073/pnas.1605063113. Epub 2016 Jul 8.

Abstract

Emotionally relevant experiences form strong and long-lasting memories by critically engaging the stress hormone/neurotransmitter noradrenaline, which mediates and modulates the consolidation of these memories. Noradrenaline acts through adrenergic receptors (ARs), of which β2-adrenergic receptors (βARs) are of particular importance. The differential anatomical and cellular distribution of βAR subtypes in the brain suggests that they play distinct roles in memory processing, although much about their specific contributions and mechanisms of action remains to be understood. Here we show that astrocytic rather than neuronal β2ARs in the hippocampus play a key role in the consolidation of a fear-based contextual memory. These hippocampal β2ARs, but not β1ARs, are coupled to the training-dependent release of lactate from astrocytes, which is necessary for long-term memory formation and for underlying molecular changes. This key metabolic role of astrocytic β2ARs may represent a novel target mechanism for stress-related psychopathologies and neurodegeneration.

Keywords: astrocyte; hippocampus; lactate; memory; β-adrenergic receptor.

Publication types

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

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / pharmacology
  • Analysis of Variance
  • Animals
  • Astrocytes / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / physiology*
  • Lactic Acid / metabolism
  • Lactic Acid / pharmacology
  • Learning / physiology
  • Male
  • Memory, Long-Term / drug effects
  • Memory, Long-Term / physiology*
  • Propanolamines / administration & dosage
  • Propanolamines / pharmacology
  • Propranolol / administration & dosage
  • Propranolol / pharmacology
  • RNA Interference
  • Rats, Long-Evans
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Time Factors

Substances

  • Adrenergic beta-Antagonists
  • Propanolamines
  • Receptors, Adrenergic, beta-2
  • Lactic Acid
  • ICI 118551
  • Propranolol