Calcium/Calmodulin-Dependent Protein Kinase II Serves as a Biochemical Integrator of Calcium Signals for the Induction of Synaptic Plasticity

Yasuda, Ryohei

Bennett, Vann

Chang, Jui-Yun

2016-09-29T14:39:44Z

2018-07-13T08:17:14Z

2016

Biochemistry

Repetitive Ca2+ transients in dendritic spines induce various forms of synaptic plasticity by transmitting information encoded in their frequency and amplitude. CaMKII plays a critical role in decoding these Ca2+ signals to initiate long-lasting synaptic plasticity. However, the properties of CaMKII that mediate Ca2+ decoding in spines remain elusive. Here, I measured CaMKII activity in spines using fast-framing two-photon fluorescence lifetime imaging. Following each repetitive Ca2+ elevations, CaMKII activity increased in a stepwise manner. This signal integration, at the time scale of seconds, critically depended on Thr286 phosphorylation. In the absence of Thr286 phosphorylation, only by increasing the frequency of repetitive Ca2+ elevations could high peak CaMKII activity or plasticity be induced. In addition, I measured the association between CaMKII and Ca2+/CaM during spine plasticity induction. Unlike CaMKII activity, association of Ca2+/CaM to CaMKII plateaued at the first Ca2+ elevation event. This result indicated that integration of Ca2+ signals was initiated by the binding of Ca2+/CaM and amplified by the subsequent increases in Thr286-phosphorylated form of CaMKII. Together, these findings demonstrate that CaMKII functions as a leaky integrator of repetitive Ca2+ signals during the induction of synaptic plasticity, and that Thr286 phosphorylation is critical for defining the frequencies of such integration.

https://hdl.handle.net/10161/12854

Biochemistry

Neurosciences

calcium signals integration

CaMKII

FLIM

frequency decoder

FRET

spine plasticity

Calcium/Calmodulin-Dependent Protein Kinase II Serves as a Biochemical Integrator of Calcium Signals for the Induction of Synaptic Plasticity

Dissertation

21