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2008年12月22日

Developmental Regulation of PSD-95 in the Central Visual System

日 時 2008年12月22日(月) 13:00
講演者 吉井 聡 博士
講演者所属 McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
お問い合わせ先 広報展開推進室 小泉 周 (内線7722)
要旨

PSD-95 is a scaffolding protein for the glutamate receptors that regulates synaptic plasticity. Eye opening (EO) is a key event during the development of the rodent visual pathway that causes a rapid increase of PSD-95 at the synapse (Yoshii et al. 2003). The increase of PSD-95 is tied to changes of synaptic function and structure that occur during the period bracketing EO. Previously, we showed that PSD-95 was transported to synapses in response to BDNF application (Yoshii and Constantine-Paton 2007). BDNF binds its receptor, TrkB which activates PI3 kinase/Akt pathway. This signaling cascade drives pan-dendritic delivery of PSD-95. While considerable details about how BDNF activates PSD-95 trafficking are known for cultured neurons, it is not known whether this trafficking mechanism occurs in vivo.

To this end, we are studying a transgenic mouse that has knock-in mutation in the TrkB receptor that has been engineered so that chemical compound 1NM-PP1 binds to this mutation site and blocks the activation of TrkB (the TrkB F616A moue; Chen et al. 2005). Using Elvax, a slow release polymer, we applied 1NM-PP1 to the surface of visual cortex before EO. The blockade of TrkB signaling suppressed a redistribution of PSD-95 associated with EO. This method will allow us to further study the role of BDNF/TrkB signaling on structural and functional changes in intact early postnatal animals. Furthermore, the correlation of molecular events at synapses to a developmental milestone will set a stage for studying neurodevelopmental disorders.

【参考文献】

  • Yoshii, Sheng and Constantine-Paton. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1334-9.
  • Yoshii and Constantine-Paton. Nat Neurosci. 2007 Jun;10(6):702-11. Chen et al. Neuron. 2005 Apr 7;46(1):13-21.