TY - JOUR
T1 - Astrocytic β2- Adrenergic receptors mediate hippocampal long- Term memory consolidation
AU - Gao, Virginia
AU - Suzuki, Akinobu
AU - Magistretti, Pierre J.
AU - Lengacher, Sylvain
AU - Pollonini, Gabriella
AU - Steinman, Michael Q.
AU - Alberini, Cristina M.
N1 - Funding Information:
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 (École Polytechnique Fédérale 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 βAR 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
PY - 2016/7/26
Y1 - 2016/7/26
N2 - 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.
AB - 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.
KW - Astrocyte
KW - Hippocampus
KW - Lactate
KW - Memory
KW - β- Adrenergic receptor
UR - http://www.scopus.com/inward/record.url?scp=84979519276&partnerID=8YFLogxK
U2 - 10.1073/pnas.1605063113
DO - 10.1073/pnas.1605063113
M3 - 学術論文
C2 - 27402767
AN - SCOPUS:84979519276
SN - 0027-8424
VL - 113
SP - 8526
EP - 8531
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 30
ER -