Mitochondrial flash signals long-term memory at neuronal synapse

JUN . 27 2017
Peking University, June 26, 2017: Why do some memories last a lifetime while others never persist for more than a few minutes? How are short-term memories converted into long-term ones? Recently, a collaborative study led by Dr. Cheng Heping and Wang Xianhua at Peking University and Dr. Bi Guo-Qiang at University of Science and Technology of China have revealed the essential role of dendritic mitochondrial flash in transforming short-term synaptic plasticity into long-term plasticity, which is known to be the cellular correlates of long-term memory. Results from the study have been published in Nature Communications (Nat. Commun., 2017, 8: 31) on June 26, 2017.
Mitochondrial flash or ‘mitoflash’ was first identified by Dr. Cheng’s team at PKU as a quantal signal at single-mitochondrion level. A mitoflash lasts for tens of seconds and consists multifaceted signals including membrane depolarization, reactive oxygen species (ROS) production, and matrix alkalization. Further, mitoflash is highly conserved and exists in functional mitochondria in all cell types examined. As an energy consuming event together with release of ROS, what is the physiological significance of mitoflash? Dr. Cheng and Dr. Wang have led their teams to pursue the biological relevance of mitoflash over the years.

Mitoflash promotes synaptic long-term potentiation
Synaptic plasticity is regarded as the cellular basis of learning and memory. Induced by different patterns of neuronal activities, short-term synaptic plasticity lasts for few seconds to a few minutes, whereas long-term plasticity lasts for tens of minutes to hours and even longer.

The researchers hypothesized that mitoflash might be involved in the signaling transduction of synaptic plasticity. To test their hypothesis, the Ph.D. students Fu Zhong-Xiao and Tan Xiao employed a classical cellular model (rat hippocampal neurons) to study learning and memory. They also developed a set of new methods including long-term continuous imaging of mitoflashes and photon-activation of individual mitoflash events by femtosecond laser pulses. Interestingly, they found that synaptic long-term potentiation was always accompanied by one or more mitoflashes in nearby dendritic mitochondria after chemical, electrical or glutamate uncaging induced LTP; furthermore, artificially induced mitoflashes could in turn facilitate transition from short-term synaptic potentiation to long-term potentiation. Intriguingly, the regulatory effect of mitoflash on synaptic plasticity was only effective within the critical time-window of 30 minutes and a spatial extent of about 2 μm, demonstrating the spatiotemporal precision of this regulatory mechanism. Further study revealed that synaptic calcium and calcium-calmodulin kinase were important for eliciting mitoflash, which in turn released ROS to signal long-term synaptic plasticity.  
This study identifies mitoflashes as digital bio-signals playing essential roles in synaptic plasticity. It reveals for the first time the bi-directional interaction between dendritic mitochondria and synapses, and provides novel insight into the biological relevance of mitoflash: local and transient ROS burst may provide a subcellular mechanism for “burning” short-term synaptic changes into long-term memory.
The co-first authors of this work are Ph.D. students Fu Zhong-Xiao and Tan Xiao, corresponding authors are Wang Xianhua (PKU), Cheng Heping (PKU) and Bi Guo-Qiang (USTC). The study was supported in part by the Strategic Priority Research Program of the Chinese Academy of Sciences, the National Basic Research Program of China, and the National Science Foundation of China.

Edited by: Zhang Jiang
Source: Institute of Molecular Medicine