2026-01-08 九州大学
図:条件づけ学習が生じる瞬間の海馬の神経活動
<関連情報>
- https://www.kyushu-u.ac.jp/ja/researches/view/1389
- https://www.kyushu-u.ac.jp/f/64373/26_0108_01.pdf
- https://www.pnas.org/doi/abs/10.1073/pnas.2519161123
海馬における連合学習のための条件刺激の神経基質 Neural substrate of conditioned stimulus for associative learning in the hippocampus
Kyogo S. Kobayashi, Ren Sogabe, Tsuyoshi Tatsukawa, +1 , and Naoki Matsuo
Proceedings of the National Academy of Sciences Published:January 9, 2026
DOI:https://doi.org/10.1073/pnas.2519161123
Significance
Pavlov demonstrated that effective conditioning requires the conditioned stimulus (CS) to slightly precede the unconditioned stimulus (US), but the underlying neural substrates that fulfill this temporal contingency have remained elusive. Here, we identified hippocampal neurons in mice whose activity could represent a CS during contextual fear conditioning. Notably, these neurons are part of the “prospective” engram cells, characterized by immediate early gene expression, such as c-fos, during learning. While engram cells have been implicated in memory representation, their real-time role at the moment of learning was unclear. Our findings provide insights into the neural mechanisms underlying associative memory formation.
Abstract
Associative learning allows animals to learn the predictive relationships between events. Presentation of a conditioned stimulus (CS) preceding an unconditioned stimulus (US) within a short interval associates these events. However, little is known about the neural substrates that represent CSs. By combining in vivo calcium imaging with retrospective identification of dorsal hippocampal CA1 neurons, in which c-fos is induced during contextual fear conditioning in mice, we found that prospective c-fos (+) neurons were activated upon novel environmental exposure. Importantly, a part of them was transiently reactivated 1 to 2 s before the shock US as well as during memory retrieval, and these activities were correlated with memory expressions. Optogenetic silencing demonstrated that timing-dependent neuronal activity is crucial for memory formation. Our study identifies a cellular substrate for the CS that underlies the CS–US temporal contiguity rule under physiological conditions and suggests how the internal representation of context serves as a CS, demonstrating the role of prospective engram cells at the moment of conditioned learning.
