Astrocytic beta(2)-adrenergic receptors mediate hippocampal long-term memory consolidation

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 beta(2)-adrenergic receptors (beta ARs) are of particular importance. The differential anatomical and cellular distribution of beta AR 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 beta(2)ARs in the hippocampus play a key role in the consolidation of a fear-based contextual memory. These hippocampal beta(2)ARs, but not beta(1)ARs, 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 beta(2)ARs may represent a novel target mechanism for stress-related psychopathologies and neurodegeneration.