title: Astrocytic β2-adrenergic receptors mediate hippocampal long-term memory consolidation.
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.
authors.affiliation: Center for Neural Science, New York University, New York, NY 10003; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Virginia
authors.initials: V
authors.lastname: Gao
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Akinobu
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia; Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland;
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Magistretti
authors.affiliation: Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland; Department of Psychiatry, Centre for Psychiatric Neuroscience, Lausanne University Hospital, 1008 Lausanne-Prilly, Switzerland.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lengacher
authors.affiliation: Center for Neural Science, New York University, New York, NY 10003;
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pollonini
authors.affiliation: Center for Neural Science, New York University, New York, NY 10003;
authors.forename: Michael Q
authors.initials: MQ
authors.lastname: Steinman
authors.affiliation: Center for Neural Science, New York University, New York, NY 10003; ca60@nyu.edu.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Alberini
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019344:Lactic Acid / Q000378:metabolism / Q000494:pharmacology; D007858:Learning / Q000502:physiology; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology*; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D034622:RNA Interference; D020318:Rats, Long-Evans; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D019344:Lactic Acid; C026777:ICI 118551; D011433:Propranolol
keywords: astrocyte; hippocampus; lactate; memory; β-adrenergic receptor