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Synaptic Plasticity

開催日 2014/9/11
時間 16:00 - 17:00
会場 Poster / Exhibition(Event Hall B)

Retrograde signaling by Sema3A and Sema7A regulates synapse elimination in the developing cerebellum

  • P1-056
  • 上阪 直史 / Naofumi Uesaka:1 内ヶ島 基政 / Motokazu Uchigashima:2 三國 貴康 / Takayasu Mikuni:1 中澤 敬信 / Takanobu Nakazawa:1 中尾 晴美 / Harumi Nakao:4 平井 宏和 / Hirokazu Hirai:3 饗場 篤 / Atsu Aiba:4 渡辺 雅彦 / Masahiko Watanabe:2 狩野 方伸 / Masanobu Kano:1 
  • 1:東京大学・医・神経生理学 / Dept. Neurophysiol., Grad Sch Med, Univ of Tokyo, Tokyo 2:北海道 大・医・解剖 / Dept. Anat., Grad Sch Med, Hokkaido Univ, Sapporo 3:群馬大学・医・神経生理学 / Dept. of Neurophysiol., Grad. Sch. of Med., Gunma Univ., Maebashi 4:東京大学・医・動物資源学 / Dept. Animal Resour., Grad Sch Med, Univ of Tokyo, Tokyo 

In the nervous systems of neonatal animals, redundant synaptic connections are present between neurons. Subsequently, unnecessary connections are weakened and eliminated, whereas necessary connections are strengthened and persistent into adulthood. This process, known as "synapse elimination", is crucial for shaping functional neural circuits and for proper brain functions. Accumulating evidence suggests that retrograde signaling from postsynaptic cells regulates synapse elimination, but the underlying mechanisms remain unknown. Here we show that two distinct semaphorins, Sema3A and Sema7A, mediate retrograde signals for elimination of redundant climbing fiber (CF) to Purkinje cell (PC) synapses in the developing cerebellum. We picked up candidate retrograde signaling molecules that are expressed in PCs and the receptors of these candidate molecules that are present in CFs during the period of CF synapse elimination. We then assessed the effects of lentivirus-mediated RNAi-knockdown of these molecules on CF synapse elimination. By this systematic screening, we found that knockdown of Sema3A in PCs or its co-receptor, plexinA4 (PlxnA4), in CFs accelerated CF synapse elimination and decreased CF-mediated synaptic inputs. In contrast, knockdown of Sema7A in PCs or either of the two receptors for Sema7A, plexinC1 (PlxnC1) and integrinB1 (ItgB1), in CFs impaired CF synapse elimination. Importantly, the effect of Sema7A involves signaling by type 1 metabotropic glutamate receptor (mGluR1), a canonical pathway in PCs for the final stage of CF synapse elimination. These findings define how semaphorins retrogradely regulate multiple processes of CF synapse elimination during postnatal cerebellar development.

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