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.
Bibliographical noteKAUST Repository Item: Exported on 2020-10-01
Acknowledgements: We thank Dr. Karl Deisseroth (Stanford University) for generously providing pAAV-hSyn plasmids; Dr. Mark Kay (Stanford University) for generously providing the pRC-DJ plasmid used to produce AAVDJ; Dr. Bernard Schneider (Ecole Polytechnic Federale de Lausanne) for generously providing the pAAV-short gfaABC1D-eGFP plasmid used to produce AAV9; and Dr. Alberto Julio Kaumann (University of Murcia) for helpful advice concerning beta AR radiolabeling. This work was supported by NIH Grant R01 MH100822 and the McKnight Memory and Cognitive Disorder Award (to C.M.A.) and NIH Grant F30 MH098570 (to V.G.).