CaMKII Autophosphorylation Is Necessary for Optimal Integration of Ca2+ Signals during LTP Induction, but Not Maintenance.

CaMKII plays a critical role in decoding calcium (Ca2+) signals to initiate long-lasting synaptic plasticity. However, the properties of CaMKII that mediate Ca2+ signals in spines remain elusive. Here, we measured CaMKII activity in spines using fast-framing two-photon fluorescence lifetime imaging. Following each pulse during repetitive Ca2+ elevations, CaMKII activity increased in a stepwise manner. Thr286 phosphorylation slows the decay of CaMKII and thus lowers the frequency required to induce spine plasticity by several fold. In the absence of Thr286 phosphorylation, increasing the stimulation frequency results in high peak mutant CaMKIIT286A activity that is sufficient for inducing plasticity. Our findings demonstrate that Thr286 phosphorylation plays an important role in induction of LTP by integrating Ca2+ signals, and it greatly promotes, but is dispensable for, the activation of CaMKII and LTP.

Relationships between Body Image, Body Mass Index, and Smoking in Korean Adolescents: Results of a Nationwide Korea Youth Risk Behavior Web-based Survey.

OBJECTIVE: This study assessed the association between subjective body image or objective body mass index (BMI) and the risk of daily smoking in Korean adolescents, with a purpose of identifying the most suitable models. MATERIALS AND METHODS: Using the 2013 9th Korea Youth Risk Behavior Web-based Survey data for 72,435 students, odds ratios were calculated for daily smoking in the past month, according to the subjective body image and calculated BMI using a respective multiple logistic regression model. The combined effect of these two factors was also analyzed by pairing a BMI category with a subjective body image category, using odds ratios for the same event within each sex group. RESULTS: Among the surveyed students, 7.2% of boys and 1.8% of girls were classified as daily smokers. Students who perceived themselves as being very obese tended to be at lower risk of daily smoking (OR=0.61 in boys with 95% CI=0.47 to 0.79; OR=0.66 in women with 95% CI=0.47 to 0.93). In addition, boys within the obese or overweight BMI category showed a lower risk of daily smoking (OR=0.86, 95% CI: 0.77-0.96). Lean BMI was significantly associated with higher odds ratios for daily smoking only in female students (OR=1.24, 95% CI: 1.02-1.52). When pairing these two objective and subjective factors, results suggested that subjective body image has a greater effect on daily smoking than BMI in both boys and girls. CONCLUSIONS: In both male and female students, subjective body image had a greater effect on daily smoking than body mass index. A model using the combination of BMI and subjective body image was the best fit in girls, in contrast to the model using subjective body image only best suitable in boys, for the prediction of daily smoking. These results including several factors associated with daily smoking in Korean students, provide useful data for the development and implementation of smoking intervention and cessation programs for adolescents.

Imaging neural activity using Thy1-GCaMP transgenic mice.

The ability to chronically monitor neuronal activity in the living brain is essential for understanding the organization and function of the nervous system. The genetically encoded green fluorescent protein-based calcium sensor GCaMP provides a powerful tool for detecting calcium transients in neuronal somata, processes, and synapses that are triggered by neuronal activities. Here we report the generation and characterization of transgenic mice that express improved GCaMPs in various neuronal subpopulations under the control of the Thy1 promoter. In vitro and in vivo studies show that calcium transients induced by spontaneous and stimulus-evoked neuronal activities can be readily detected at the level of individual cells and synapses in acute brain slices, as well as chronically in awake, behaving animals. These GCaMP transgenic mice allow investigation of activity patterns in defined neuronal populations in the living brain and will greatly facilitate dissecting complex structural and functional relationships of neural networks.

Activation of CaMKII in single dendritic spines during long-term potentiation.

Calcium/calmodulin-dependent kinase II (CaMKII) plays a central part in long-term potentiation (LTP), which underlies some forms of learning and memory. Here we monitored the spatiotemporal dynamics of CaMKII activation in individual dendritic spines during LTP using two-photon fluorescence lifetime imaging microscopy, in combination with two-photon glutamate uncaging. Induction of LTP and associated spine enlargement in single spines triggered transient ( approximately 1 min) CaMKII activation restricted to the stimulated spines. CaMKII in spines was specifically activated by NMDA receptors and L-type voltage-sensitive calcium channels, presumably by nanodomain Ca(2+) near the channels, in response to glutamate uncaging and depolarization, respectively. The high degree of compartmentalization and channel specificity of CaMKII signalling allow stimuli-specific spatiotemporal patterns of CaMKII signalling and may be important for synapse-specificity of synaptic plasticity.

Spatiotemporal Regulation of Signaling in and out of Dendritic Spines: CaMKII and Ras.

Recent advances in 2-photon fluorescence lifetime imaging microscopy (2pFLIM) in combination with 2-photon photochemistry have enabled the visualization of neuronal signaling during synaptic plasticity at the level of single dendritic spines in light scattering tissue. Using these techniques, the activity of Ca(2+)/Calmodulin-dependent kinase II (CaMKII) and Ras have been imaged in single spines during synaptic plasticity and associated spine enlargement. These provide two contrasting examples of spatiotemporal regulation of spine signaling: Ras signaling is diffusive and spread over ~10 µm along the dendrites, while CaMKII activation is restricted to the spine undergoing plasticity. In this review, we will discuss the mechanisms and roles of the different spatiotemporal regulation of signaling in neurons, and the impact of the spine structure upon these biochemical signaling processes.