美国马克斯·普朗克佛罗里达神经科学研究所Ryohei Yasuda团队近期取得重要工作进展，他们研究提出了行为时间尺度可塑性中的树突、延迟、随机CaMKII激活。相关研究成果2024年10月9日在线发表于《自然》杂志上。

据介绍，行为时间尺度可塑性（BTSP）是通过整合由行为相关时间尺度（秒）分隔的，突触前和突触后成分而诱导的非Hebbian可塑性。海马CA1神经元中的BTSP是定位细胞形成的基础。然而，在行为时间尺度上实现突触特异性可塑性的分子机制尚不清楚。

研究人员表明，使用双光子谷氨酸释放与突触后电流注射在行为时间尺度上暂时分开，可以在单个树突棘中诱导BTSP。使用改进的Ca²⁺/钙调素依赖性激酶II（CaMKII）传感器，研究人员在BTSP诱导过程中没有检测到CaMKII的激活。相反，在BTSP诱导后10-100秒观察到与Ca²⁺内流和平台电位相关的树突、延迟和随机CaMKII激活（DDSC）。DDSC需要突触前和突触后活动，这表明CaMKII可以整合这两种信号。

此外，在BTSP协议后15-30秒，光遗传学阻断CaMKII抑制了突触增强，这表明DDSC是BTSP的重要机制。IP₃依赖的细胞内Ca²⁺释放促进了DDSC和BTSP。

因此，这一研究表明，在BTSP期间，非突触特异性CaMKII激活提供了一个具有数十秒宽时间窗口的指导性信号。

附：英文原文

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

Author: Jain, Anant, Nakahata, Yoshihisa, Pancani, Tristano, Watabe, Tetsuya, Rusina, Polina, South, Kelly, Adachi, Kengo, Yan, Long, Simorowski, Noriko, Furukawa, Hiro, Yasuda, Ryohei

Issue&Volume: 2024-10-09

Abstract: 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 kinaseII (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 10–100s after BTSP induction. DDSC required both presynaptic and postsynaptic activity, which suggests that CaMKII can integrate these two signals. Also, optogenetically blocking CaMKII 15–30s 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.

DOI: 10.1038/s41586-024-08021-8

Source: https://www.nature.com/articles/s41586-024-08021-8