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?-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 ?-adrenergic receptors (?ARs), 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 ?AR 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 ?AR activity during, but not following PTC sets in motion cascading molecular events for the acquisition (AMPARs) and subsequent consolidation (ERK) of learned associations.

SUBMITTER: Schiff HC

PROVIDER: S-EPMC5312069 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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β-Adrenergic Receptors Regulate the Acquisition and Consolidation Phases of Aversive Memory Formation Through Distinct, Temporally Regulated Signaling Pathways.

Schiff Hillary C HC Johansen Joshua P JP Hou Mian M Bush David E A DE Smith Emily K EK Klein JoAnna E JE LeDoux Joseph E JE Sears Robert M RM

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20161020 4

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 ...[more]

PMID: 27762270

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Project description:Study objectivesSleep during the biological night facilitates memory consolidation. Here we determined the impact of sleep and wake on motor skill learning (acquisition) and subsequent off-line skill improvement (memory consolidation), independent of circadian phase, and compared this to the impact of the endogenous circadian system, independent of whether sleep occurred during the biological night or day.MethodsParticipants completed two 8-day sleep laboratory visits, adhering on one visit to a circadian aligned ("normal") sleep schedule for the full duration of the protocol, and on the other to a circadian misaligned (12-hour inverted) schedule, with alignment during the first 3 days, a 12-hour 'slam shift' on Day 4, followed by circadian misalignment during the last 4 days of the protocol. Participants were repeatedly trained and tested on different versions of the finger-tapping motor sequence task across each visit.ResultsSleep facilitated offline memory consolidation regardless of whether it occurred during the biological day or night, while circadian phase had no significant impact. These sleep-related benefits remained after accounting for general motor speed, measured in the absence of learning. In addition, motor skill acquisition was facilitated when the training session followed shortly after sleep, without significant impact of circadian phase (biological morning vs. evening). This effect was largely driven by heightened acquisition in participants who slept during the day and were trained shortly thereafter, that is, when acquisition occurred during the biological evening. These benefits were also retained after controlling for general motor speed.ConclusionsSleep benefits both the acquisition and consolidation of motor skill regardless of whether they occur during the biological day or night. After controlling for general motor speed, a critical adjustment that few studies perform, these sleep benefits remain intact. Our findings have clear implications for night shift workers who obtain their sleep during the day.

Dataset Information

?-Adrenergic Receptors Regulate the Acquisition and Consolidation Phases of Aversive Memory Formation Through Distinct, Temporally Regulated Signaling Pathways.

Publications

β-Adrenergic Receptors Regulate the Acquisition and Consolidation Phases of Aversive Memory Formation Through Distinct, Temporally Regulated Signaling Pathways.

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