title: β-Adrenergic Receptors Regulate the Acquisition and Consolidation Phases of Aversive Memory Formation Through Distinct, Temporally Regulated Signaling Pathways.
abstract: Memory formation requires the temporal coordination of molecular events and cellular processes following a learned event. During Pavlovian threat (fear) conditioning (PTC), sensory and neuromodulatory inputs converge on post-synaptic neurons within the lateral nucleus of the amygdala (LA). By activating an intracellular cascade of signaling molecules, these G-protein-coupled neuromodulatory receptors are capable of recruiting a diverse profile of plasticity-related proteins. Here we report that norepinephrine, through its actions on β-adrenergic receptors (βARs), modulates aversive memory formation following PTC through two molecularly and temporally distinct signaling mechanisms. Specifically, using behavioral pharmacology and biochemistry in adult rats, we determined that βAR activity during, but not after PTC training initiates the activation of two plasticity-related targets: AMPA receptors (AMPARs) for memory acquisition and short-term memory and extracellular regulated kinase (ERK) for consolidating the learned association into a long-term memory. These findings reveal that βAR activity during, but not following PTC sets in motion cascading molecular events for the acquisition (AMPARs) and subsequent consolidation (ERK) of learned associations.
authors.affiliation: Center for Neural Science, New York University, New York, NY, USA.
authors.forename: Hillary C
authors.initials: HC
authors.lastname: Schiff
authors.affiliation: RIKEN Brain Science Institute, Laboratory for Neural Circuitry of Memory, Wako-shi, Saitama, Japan.|Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Johansen
authors.affiliation: Center for Neural Science, New York University, New York, NY, USA.
authors.forename: Mian
authors.initials: M
authors.lastname: Hou
authors.affiliation: Center for Neural Science, New York University, New York, NY, USA.
authors.forename: David E A
authors.initials: DE
authors.lastname: Bush
authors.affiliation: Center for Neural Science, New York University, New York, NY, USA.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Smith
authors.affiliation: Center for Neural Science, New York University, New York, NY, USA.
authors.forename: JoAnna E
authors.initials: JE
authors.lastname: Klein
authors.affiliation: Center for Neural Science, New York University, New York, NY, USA.|Department of Psychology, New York University, New York, NY, USA.|Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: LeDoux
authors.affiliation: Center for Neural Science, New York University, New York, NY, USA.|Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.|Department of Child and Adolescent Psychiatry, New York University School of Medicine, New York, NY, USA.
authors.forename: Robert M
authors.identifier: http://orcid.org/0000-0001-5688-1853
authors.initials: RM
authors.lastname: Sears
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005239:Fear / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D011943:Receptors, Adrenergic, beta; D048049:Extracellular Signal-Regulated MAP Kinases; D009638:Norepinephrine