A critical role for CaMKII in behavioral timescale synaptic plasticity in hippocampal CA1 pyramidal neurons.

Kuo Xiao, Yiding Li, Raymond A Chitwood, Jeffrey C Magee

Science advances 2023 Sep 08

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Behavioral timescale synaptic plasticity (BTSP) is a type of non-Hebbian synaptic plasticity reported to underlie place field formation. Despite this important function, the molecular mechanisms underlying BTSP are poorly understood. The α-calcium-calmodulin-dependent protein kinase II (αCaMKII) is activated by synaptic transmission-mediated calcium influx, and its subsequent phosphorylation is central to synaptic plasticity. Because the activity of αCaMKII is known to outlast the event triggering phosphorylation, we hypothesized that it could mediate the extended timescale of BTSP. To examine the role of αCaMKII in BTSP, we performed whole-cell in vivo and in vitro recordings in CA1 pyramidal neurons from mice engineered with a point mutation at the autophosphorylation site (T286A) causing accelerated signaling kinetics. Here, we demonstrate a profound deficit in synaptic plasticity, strongly suggesting that αCaMKII signaling is required for BTSP. This study elucidates part of the molecular mechanism of BTSP and provides insight into the function of αCaMKII in place cell formation and ultimately learning and memory.

Citation

Kuo Xiao, Yiding Li, Raymond A Chitwood, Jeffrey C Magee. A critical role for CaMKII in behavioral timescale synaptic plasticity in hippocampal CA1 pyramidal neurons. Science advances. 2023 Sep 08;9(36):eadi3088