Dendritic, delayed, stochastic CaMKII activation in behavioural time scale plasticity

• 成果类型: Article
• 署名作者: Jain, Anant; Nakahata, Yoshihisa; Pancani, Tristano; Watabe, Tetsuya; Rusina, Polina; South, Kelly; Adachi, Kengo; Yan, Long; Simorowski, Noriko; Furukawa, Hiro; Yasuda, Ryohei
• 署名单位: Max Planck Society; Cold Spring Harbor Laboratory
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4678
• DOI: 10.1038/s41586-024-08021-8
• 发表日期: 2024-11-07
• 关键词: long-term potentiation; kinase-ii; autophosphorylation; mechanisms; cultures; neurons; ltp

摘要

Behavioural time scale plasticity (BTSP) is non-Hebbian plasticity induced by integrating presynaptic and postsynaptic components separated by a behaviourally relevant time scale (seconds)1. BTSP in hippocampal CA1 neurons underlies place cell formation. However, the molecular mechanisms that enable synapse-specific plasticity on a behavioural time scale are unknown. Here we show that BTSP can be induced in a single dendritic spine using two-photon glutamate uncaging paired with postsynaptic current injection temporally separated by a behavioural time scale. Using an improved Ca2+/calmodulin-dependent kinase II (CaMKII) sensor, we did not detect CaMKII activation during this BTSP induction. Instead, we observed dendritic, delayed and stochastic CaMKII activation (DDSC) associated with Ca2+ influx and plateau potentials 10-100 s after BTSP induction. DDSC required both presynaptic and postsynaptic activity, which suggests that CaMKII can integrate these two signals. Also, optogenetically blocking CaMKII 15-30 s after the BTSP protocol inhibited synaptic potentiation, which indicated that DDSC is an essential mechanism of BTSP. IP3-dependent intracellular Ca2+ release facilitated both DDSC and BTSP. Thus, our study suggests that non-synapse-specific CaMKII activation provides an instructive signal with an extensive time window over tens of seconds during BTSP. Induction of behavioural time scale plasticity leads to dendritic, delayed and stochastic Ca2+/calmodulin-dependent kinase II activation, findings that clarify the mechanisms that underlie place cell formation.