Neuronal morphogenesis and activity induced neuronal plasticity are accomplished by the structural remodeling of neurons, including turnover of synapses and synaptic proteins. The underlying molecular mechanisms of the activity dependent proteolysis is not clear. This proposal investigates the non-apoptotic functions of caspases in neuronal plasticity. The experiments in this proposal will use time-lapse imaging to observe the development of cultured hippocampal neurons in order to examine whether altered caspase activity influences axon, dendrite and spine development. Immunocytochemistry and biochemical fractionation will be used to determine the subcellular distribution of caspases in neurons. To study the signals that regulate caspases during neuronal plasticity, FRET(Fluoresence Energy Transfer) will be used to examine the spatial and temporal activation of caspases upon stimulation, such as depolarization. These experiments will provide new insights about the non-apoptotic functions of caspases in neurons.
| Li, Zheng; Jo, Jihoon; Jia, Jie-Min et al. (2010) Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization. Cell 141:859-71 |
| Li, Zheng; Okamoto, Ken-Ichi; Hayashi, Yasunori et al. (2004) The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119:873-87 |
