期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2210478119
关键词
ERK; phosphatase; long-term facilitation; PKA; intertrial interactions
资金
- NIH [1R01MH12030001A1]
Two-trial learning in Aplysia reveals nonlinear interactions between training trials, where long-term memory is induced only when weak pulses precede strong ones, possibly representing a physiological mechanism to prioritize memory of escalating threats.
Two-trial learning in Aplysia reveals nonlinear interactions between training trials: A single trial has no effect, but two precisely spaced trials induce long-term memory. Extracellularly regulated kinase (ERK) activity is essential for intertrial interactions, but the mechanism remains unresolved. A combination of immunochemical and optogenetic tools reveals unexpected complexity of ERK signaling during the induction of long-term synaptic facilitation by two spaced pulses of serotonin (5-hydroxytryptamine, 5HT). Specifically, dual ERK phosphorylation at its activating TxY motif is accompanied by dephosphorylation at the pT position, leading to a buildup of inactive, singly phosphorylated pY-ERK. Phosphorylation and dephosphorylation occur concurrently but scale differently with varying 5HT concentrations, predicting that mixed two-trial protocols involving both strong and weak 5HT pulses should be sensitive to the precise order and timing of trials. Indeed, long-term synaptic facilitation is induced only when weak pulses precede strong, not vice versa. This may represent a physiological mechanism to prioritize memory of escalating threats.
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