Retrograde Signaling for Climbing Fiber Synapse Elimination
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- 作者：Naofumi Uesaka (1)
Motokazu Uchigashima (2)
Takayasu Mikuni (1)
Hirokazu Hirai (3)
Masahiko Watanabe (2)
Masanobu Kano (1) - 关键词：Climbing fiber ; Purkinje cell ; Synapse elimination ; Postnatal development ; Retrograde signal ; Semaphorin
- 刊名：The Cerebellum
- 出版年：2015
- 出版时间：February 2015
- 年：2015
- 卷：14
- 期：1
- 页码：4-7
- 全文大小：354 KB
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14. Kano M, Hashimoto K, Kurihara H, Watanabe M, Inoue Y, Aiba A, et al. Persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking mGluR1. Neuron. 1997;18:71鈥?. CrossRef
15. Pasterkamp RJ, Giger RJ. Semaphorin function in neural plasticity and disease. Curr Opin Neurobiol. 2009;19:263鈥?4. CrossRef - 作者单位：Naofumi Uesaka (1)
Motokazu Uchigashima (2)
Takayasu Mikuni (1)
Hirokazu Hirai (3)
Masahiko Watanabe (2)
Masanobu Kano (1)
1. Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
2. Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan
3. Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan - 刊物主题：Neurosciences; Neurology; Neurobiology;
- 出版者：Springer US
- ISSN：1473-4230
文摘
Neurons form exuberant synapses with target cells early in development. Then, necessary synapses are selectively strengthened whereas unnecessary connections are weakened and eventually eliminated during postnatal development. This process is known as synapse elimination and is a crucial step for shaping immature neural circuits into functionally mature versions. Accumulating evidence suggests that retrograde signaling from postsynaptic cells regulates synapse elimination, but the underlying mechanisms remain unknown. Here, we show that semaphorin3A (Sema3A) and semaphorin7A (Sema7A) mediate retrograde signals for elimination of redundant climbing fiber (CF) to Purkinje cell (PC) synapses in the developing cerebellum, a representative model of synapse elimination in the central nervous system. We picked up candidate retrograde signaling molecules that are expressed in PCs during the period of CF synapse elimination and the receptors of these candidate molecules that are present in CFs. 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. Conversely, 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 results demonstrate that specific semaphorins act as retrograde signaling molecules and regulate distinct processes of CF synapse elimination during postnatal cerebellar development.