７月下旬の日本神経科学学会に先立って、フロリダマックスプランク研究所の安田涼平先生が生理研に立ち寄られます。その際に下記日時で所長招聘セミナーを開催いたしますので、多数ご参加下さいますようご案内申し上げます。

In the central nervous system, most excitatory synapses terminate on dendritic spines, tiny (~0.1 femtoliter) protrusions emanating from the dendritic surface. Calcium influx into spines activates signaling networks composed of tens of species of molecules to induce diverse forms of synaptic plasticity, which is thought to underlie learning and memory. Although many of the molecules required for synaptic plasticity have been identified, signaling mechanisms by which calcium dynamics are decoded and translated into specific cell responses are unknown. To further our understanding of signaling mechanisms underlying synaptic plasticity, we have developed a technique to monitor signaling activity in single dendritic spines in light scattering brain slices using 2-photon fluorescence lifetime imaging (2pFLIM) in combination with new FRET sensor extensively optimized for 2pFLIM. Further, combining this technique with 2-photon glutamate uncaging greatly allowed us to image signaling activity while inducing plasticity in single dendritic spines. Using these techniques, we succeeded in monitoring activity of signaling proteins CaMKII, Ras, Rac, RhoA, Cdc42, PKC, ERK and TrkB during synaptic potentiation and associated spine enlargement induced at a single spine. Our results indicated that signaling are transmitted in multiple steps: first, short Ca²⁺ elevation (~0.1 s) is integrated by CaMKII which decays over ~5 s. This signal is further relayed by slower small GTPase proteins Ras, Rac, RhoA and Cdc42, which decays over 10-30 min.  Interestingly, stimulation of a single spine causes BDNF release from the stimulated spine and activates TrkB (BDNF receptor) on the same spine in an autocrine manner. Furthermore, this autocrine TrkB activation regulates activation of Rho GTPase proteins Rac and Cdc42 in the spine. Overall, the signal imaging techniques provide new insights into the spatiotemporal organization of biochemical computation in dendritic spines and surrounding area during synaptic plasticity.