Dendritic, delayed, and stochastic CaMKII activation underlies behavioral time scale plasticity in CA1 synapses

Jain, Anant, Nakahata, Yoshihisa, Watabe, Tetsuya, Rusina, Polina, South, Kelly, Adachi, Kengo, Yan, Long, Simorowski, Noriko, Furukawa, Hiro, Yasuda, Ryohei (August 2023) Dendritic, delayed, and stochastic CaMKII activation underlies behavioral time scale plasticity in CA1 synapses. (Submitted)

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Abstract

Behavioral time scale plasticity (BTSP), is a form of non-Hebbian plasticity induced by integrating pre- and postsynaptic components separated by behavioral time scale (seconds). BTSP in the hippocampal CA1 neurons underlies place cell formation. However, the molecular mechanisms underlying this behavioral time scale (eligibility trace) and synapse specificity are unknown. CaMKII can be activated in a synapse-specific manner and remain active for a few seconds, making it a compelling candidate for the eligibility trace during BTSP. Here, we show that BTSP can be induced in a single dendritic spine using 2-photon glutamate uncaging paired with postsynaptic current injection temporally separated by behavioral time scale. Using an improved CaMKII sensor, we saw no detectable CaMKII activation during this BTSP induction. Instead, we observed a dendritic, delayed, and stochastic CaMKII activation (DDSC) associated with Ca 2+ influx and plateau 20-40 s after BTSP induction. DDSC requires both pre-and postsynaptic activity, suggesting that CaMKII can integrate these two signals. Also, optogenetically blocking CaMKII 30 s after the BTSP protocol inhibited synaptic potentiation, indicating that DDSC is an essential mechanism of BTSP. IP3-dependent intracellular Ca 2+ release facilitates both DDSC and BTSP. Thus, our study suggests that the non-synapse specific CaMKII activation provides an instructive signal with an extensive time window over tens of seconds during BTSP.

Item Type:	Paper
CSHL Authors:	Simorowski, Noriko Furukawa, Hiro
Communities:	CSHL labs > Furukawa lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	1 August 2023
Date Deposited:	21 Sep 2023 17:23
Last Modified:	21 Sep 2023 17:23
PMCID:	PMC10418109
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/40944

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