記憶形成の新たなメカニズムを発見 Study Reveals Newly Discovered Nuances of Memory Formation
2022-09-26 ニューヨーク大学 (NYU)
NYU scientists studied Aplysia californica, the California sea slug, in shedding new light on the nature of long-term memories. Photo credit: Natalie Ruffing/Getty Images
研究チームは、ウミウシが通常実験で用いる軽い電気ショックなどの刺激に対して示す反応を再現した化学パルスを繰り返し与えて、これらのニューロンを「訓練」した。その後、ニューロン間の結合が長期的に強化される様子を観察し、長期記憶の形成を模倣し、観察した。
これらの実験の一部として、研究者達は、記憶に必要なERKというタンパク質の結果としての活性を特に調べた。
研究チームは、ERKを活性化する分子(したがって記憶に有利)と不活性化する分子(したがって記憶に不利)の間の「綱引き」という、より複雑な力学を見いだした。
研究チームは、1回の試行で、「綱引き」によって不活性化された側の分子が優勢になり、ERKの活性が停止して記憶の形成が妨げられたと述べている。一方、ERK活性の低下を防ぐには2回目の試行が必要であり、その結果、記憶が定着するようになった。
<関連情報>
- https://www.nyu.edu/about/news-publications/news/2022/september/long-term-memories-a-matter-of-order-not-just-repetition.html
- https://www.pnas.org/doi/10.1073/pnas.2210478119
ERKのリン酸化/脱リン酸化の正確なタイミングが、長期記憶形成時の試行反復の結果を決定する Precise timing of ERK phosphorylation/dephosphorylation determines the outcome of trial repetition during long-term memory formation
Nikolay V. Kukushkin, Tasnim Tabassum and Thomas J. Carew
Proceedings of the National Academy of Sciences Published:September 26, 2022
DOI:https://doi.org/10.1073/pnas.2210478119
Significance
Repetition is a fundamental feature of memory induction. According to the prevailing view, during memory induction, individual stimuli produce only short-lived, subthreshold effects in neurons, which, upon repetition, summate, build up, and eventually result in long-term memory. In our work, we present evidence that this view is incomplete: Rather than producing identical subthreshold effects, training trials can have distinct functional roles, such as “priming” and “confirmation,” depending on their position in a sequence. During the induction of long-term synaptic plasticity in Aplysia, strong stimuli can play both roles, whereas weak stimuli can only be priming but not confirming. We propose that this represents a mechanism to encode not only repetition but also escalation of potentially threatening stimuli.
Abstract
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.
