“Dynamics and mechanisms of neuronal circuit refinement in the somatosensory cortex of the neonatal mice”

Higher brain function in the mammals relies on their complex yet sophisticated neuronal circuits, which are developed in an activity-dependent manner during postnatal stages. However, the dynamics and mechanisms of neuronal circuit refinement in the developing brain are largely unknown. We are addressing the question using the mouse somatosensory cortex (barrel cortex) as a model. We have developed two novel systems for the purpose, the Supernova system, which enables sparse cortical neuron labeling and labeled-neuron specific gene manipulation in the brain, and the TCA-GFP mice, which label thalamocortical axons (TCAs) by GFP in vivo. By combining these two systems and two-photon microscopy, we have achieved 18 hour-long in vivo time-lapse imaging of normal and impaired thalamocortical circuit reorganization (dendritic refinement of cortical layer 4 neurons) starting at postnatal day 5 (P5) (Mizuno et al., Neuron 2014). We are now challenging longer term of imaging starting at an earlier developmental stage. Our novel approach should shed light on cellular and molecular mechanisms of cortical circuit reorganization during early postnatal period.

 
Recent Publications
1. Iwata, R., Matsukawa, H., Yasuda, K., Mizuno, H., Itohara, S., Iwasato, T. (2015) Developmental RacGAPa 2-chimaerin signaling is a determinant of the morphological features of dendritic spines in adulthood. Nerurosci. 35, 13728-44.
2. Suzuki, A., Lee, L.J., Hayashi, Y., Muglia, L., Itohara, S., Erzurumlu, R.S., & Iwasato, (2015) Thalamic adenylyl cyclase 1 is required for barrel formation in the somatosensory cortex. Neurosci. 290, 518-529.
3. Mizuno, H., Luo, W., Tarusawa, E., Saito, Y.M., Sato, T., Yoshimura, Y., Itohara, S., & Iwasato, T. (2014) NMDAR-Regulated Dynamics of Layer 4 Neuronal Dendrites during Thalamocortical Reorganization in Neonates.　Neuron 82, 365-379.
4. Iwata, R., Ohi, K., Kobayashi, Y., Masuda, A., Iwama, M., Yasuda, Y., Yamamori, H., Tanaka, M., Hashimoto, R., Itohara, S. & Iwasato, T. (2014) RacGAP a2 chimaerin function in development adjusts cognitive ability in adulthood. Cell Rep. 8, 1257-1264.
5. Arakawa, H., Suzuki, A., Zhao, S., Tsytsarev, V., Lo, F-S. Hayashi, Y., Itohara, S., Iwasato, T., & Erzurumlu, R.S. (2014) Thalamic NMDA receptor function is necessary for patterning of the thalamocrotical somatosensory map and for sensorimotor behaviors. J. Neurosci. 34, 12001-12014.

Posted:2016/03/10