Roles Of Dendritic Mitoflashes In Synaptic Plasticity

Dendritic spines are important loci of synaptic plasticity and their long term morphological changes are considered as structural correlates of long term memory.Processes that are essential for spine structural plasticity,like gene transcription,protein translation and receptor endocytosis/exocytosis are mainly conducted by subcellular organelles.Also as an important organelle,however,the role of mitochondria in spine structural plasticity remains elusive.Mitoflash is a new single mitochondrion level biological phenomenon,first found in cardiac myocytes when locating cpYFP fluorescent protein in mitochondrial matrix.Further investigation show that mitoflash was a multifaceted complex phenomenon and might play signaling roles both in physiological and pathological processes.However,the characteristics and function of mitoflash in neurons are still elusive.Using cultured hippocampal neuron system,we first systematically investigated mitoflash characteristics and then explored its function in synaptic structural plasticity with chemical long term potentiation induction method.In this work,to more deeply dissect the function of mitoflash in spine structural plasticity,we established the precise glutamate uncaging method,and investigated mitoflash activity and function during single spine structural-LTP and related molecular signaling pathway.By combining different glutamate uncaging methods,we found that spine long term enlargement,rather than short term enlargement,was accompanied by local dendritic mitoflash frequency increase.Also spine structural-LTP amplitude was positively correlated with local dendritic mitoflash frequency.The increase of mitoflash frequency was dependent on CaMKII activation but not protein synthesis.To further explore the function of mitoflash in structural plasticity,we increased mitoflash frequency with different methods after weak glutamate uncaging induced spine short term plasticity.First,we found that glutamate uncaging induced short term spine enlargement was converted into long term enlargement when increasing mitoflash frequency with nigericin.When increasing mitoflash frequency at single nearby mitochondrion level with laser trigger,spine short term enlargement could also be turned to long term enlargement.Furthermore,by changing the time point and location of laser triggered mitoflash,we found that mitoflash could only support spine structural-LTP within 30min after uncaging and its fuctional spatial decay constant was about 2um.On the other hand,inhibiting mitoflash frequency increase with ROS scavenger could abolish strong uncaging spine long term enlargement.In summary,we found a new biological phenomenon mitoflash that was both necessary and sufficient for converting spine short term enlargement into long term enlargement.Mitoflash supported spine long term enlargement in a precise spatio-temporal manner.Mitoflash regulated spine structural-LTP by frequency modulation and maybe through local ROS signaling pathway.