Elimination of early-formed redundant synapses during postnatal development is essential for functional neural circuit formation. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs). During postnatal development, a single CF is selectively strengthened in each PC and becomes a “winner” CF that is presumed to remain into adulthood, whereas the other “loser” CFs are eliminated. These developmental changes are dependent on neural activity and signal cascades in postsynaptic PCs. Several molecules essential for CF synapse elimination have been identified in postsynaptic PCs. Importantly, we have recently uncovered that Semaphorin3A (Sema3A) and Semaphorin7A (Sema7A) derived from postsynaptic PCs act retrogradely onto presynaptic CFs and regulate CF synapse elimination. We demonstrate that Sema3A strengthens and maintains CF synapses from postnatal day 8 (P8) to P18 and opposes the force of CF elimination. In contrast, Sema7A facilitates elimination of weaker CFs from PC somata after P15. In the continuing studies, we searched for molecules that mediate these retrograde semaphorin signals in presynaptic CFs. This short article describes how Sema3A strengthens and maintains, whereas Sema7A promotes elimination of CF synapses through respective receptors and downstream molecules in presynaptic CFs during postnatal cerebellar development.
Climbing fiber Purkinje cell Synapse elimination Retrograde signal Semaphorin
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We thank K. Matsuyama, M. Sekiguchi, and M. Baba for the technical assistance. This work was supported by Grants-in-Aid for Scientific Research (15H05568 to N.U., 25000015 to M.K.) from JSPS, Japan, and by Brain/MINDS from MEXT and AMED, Japan and SRPBS from AMED, Japan.
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Conflict of Interest
The authors declare that there are no conflicts of interest in the submission of this manuscript to The Cerebellum.
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