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Retrograde signaling for climbing fiber synapse elimination
Naofumi Uesaka1, Motokazu Uchigashima, Takayasu Mikuni
1Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Cerebellum (London, England)
|October 24, 2014
Summary
Semaphorins 3A and 7A act as retrograde signals to eliminate redundant climbing fiber synapses in the developing cerebellum. This research identifies key molecules regulating neural circuit refinement during postnatal development.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Signaling
Background:
- Synapse elimination is critical for mature neural circuits.
- Retrograde signaling from postsynaptic cells is implicated but poorly understood.
Purpose of the Study:
- To identify retrograde signaling molecules regulating synapse elimination.
- To elucidate the mechanisms of climbing fiber (CF) to Purkinje cell (PC) synapse elimination in the developing cerebellum.
Main Methods:
- Systematic screening of candidate retrograde signaling molecules in PCs.
- Assessed effects of lentivirus-mediated RNAi-knockdown in PCs and CFs.
- Investigated semaphorin signaling pathways and their receptors.
Main Results:
- Semaphorin3A (Sema3A) knockdown accelerated CF synapse elimination.
- Semaphorin7A (Sema7A) knockdown impaired CF synapse elimination.
- Sema7A's effect involves metabotropic glutamate receptor 1 (mGluR1) signaling.
Conclusions:
- Specific semaphorins (Sema3A, Sema7A) function as retrograde signals for CF synapse elimination.
- These molecules regulate distinct phases of synapse elimination in the developing cerebellum.
- Identified key molecular players in neural circuit refinement.
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