“Regulatory mechanism of neuronal circuit shift by activity-dependent gene expression in the neocortex”

During development, fundamental neuronal circuits are formed by a genetically defined program, but the fine structure is established by environmental stimuli, stimulus-evoked neuronal activity such as action potentials and synaptic responses. Axon branching, which determines the circuit property, is affected strongly by the activity-dependent process. We have studied the activity-dependent mechanism, focusing on branch formation of thalamocortical axons. Our previous studies have demonstrated that neuronal activity promotes axon branching, and that both pre- and post-synaptic cell activity are required for branch formation. Moreover, we have shown that Netrin-4 is expressed by cortical cells in an activity-dependent fashion, and promotes thalamocortical axon branching. Our recent evidence further suggests that a cortical cell-derived factor acts as a negative regulator, whose expression is suppressed by neuronal activity. Thus, we have revealed the cellular and molecular mechanisms which underlie activity-dependent axon branching. However, the mechanisms of the activity-dependent molecular expression and the actions of the effector molecules are largely unknown. First, we study what neuronal activity efficiently controls the molecular expression from the physiological point of view. Second, we investigate the transcription regulation from the molecular biological point of view. Third, the spatiotemporal action of the effector molecules is investigated. We would like to give an insight into the mechanisms by which environmental stimuli modify neuronal circuits during development.

Recent Publications
1. Yamada, A., Uesaka, N., Hayano, Y., Tabata., T, Kano M. & Yamamoto, N. Role of pre- and postsynaptic activity in thalamocortical axon branching. Proc Natl Acad Sci. U S A, 107: 7562-7567. (2010)
2. Hayano, Y., Sasaki, K., Ohmura, N., Takemoto, M., Maeda, Y., Yamashita, T., Hata, Y., Kitada, K. & Yamamoto, N. Netrin-4 regulates thalamocortical axon branching in an activity-dependent fashion. Proc Natl Acad Sci. U S A 111, 15226-31. (2014)
3. Sugo, N., Morimatsu, M., Arai, Y., Kousoku, Y., Ohkuni, A., Nomura, T., Yanagida, T., & Yamamoto, N. Single-molecule imaging reveals dynamics of CREB transcription factor bound to its target sequence. Sci. Rep 5:10662. (2015)

Posted:2016/03/10