ArticleProceedings of the National Academy of Sciences of the United States of America2016
Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 89 citations in OpenAlex.
- Molecular and Cellular Mechanisms of Synaptogenesis and Synaptic Refinement During Cerebellar Circuit Formation.International journal of molecular sciences · 2026Review
- Loss of YY1 in Purkinje cells triggers cerebellar ataxia via Wnt10b-mediated impairment of dendrite development.iScience · 2026Article
- Incomplete cerebellar circuit restoration limits functional recovery following SMN therapy in severe spinal muscular atrophy.bioRxiv : the preprint server for biology · 2026Article
- Enhanced mGluR1 function causes motor deficits and region-specific Purkinje cell dysfunction.Brain : a journal of neurology · 2026Article
- mGluR1 signaling is necessary for strengthening winner climbing fiber inputs in the developing mouse cerebellum.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A New Class of Vitamin K Analogues Containing the Side Chain of Retinoic Acid Have Enhanced Activity for Inducing Neuronal Differentiation.ACS chemical neuroscience · 2025Article
- The transcription factor ZFP64 promotes activity-dependent synapse elimination during postnatal cerebellar development.iScience · 2025Article
- Article
- Molecular and Anatomical Strengthening of "Winner" Climbing Fiber Synapses in Developing Mouse Purkinje Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Stepwise molecular specification of excitatory synapse diversity onto cerebellar Purkinje cells.Nature neuroscience · 2025Article
- Article
- CB1R activates the epilepsy-associated protein Go to regulate neurotransmitter release and synaptic plasticity in the cerebellum.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Bioorthogonal chemical labeling of endogenous neurotransmitter receptors in living mouse brains.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Neuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation.Nature communications · 2024Article
- Molecular and cellular mechanisms of developmental synapse elimination in the cerebellum: Involvement of autism spectrum disorder-related genes.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2024Review
- Article
- Pre-ataxic loss of intrinsic plasticity and motor learning in a mouse model of SCA1.Brain : a journal of neurology · 2023Article
- cAMP-EPAC-PKCε-RIM1α signaling regulates presynaptic long-term potentiation and motor learning.eLife · 2023Article
- Disruptive lysosomal-metabolic signaling and neurodevelopmental deficits that precede Purkinje cell loss in a mouse model of Niemann-Pick Type-C disease.Scientific reports · 2023Article
- Regulation of cerebellar network development by granule cells and their molecules.Frontiers in molecular neuroscience · 2023Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In Purkinje cells (PCs) of the cerebellum, a single "winner" climbing fiber (CF) monopolizes proximal dendrites, whereas hundreds of thousands of parallel fibers (PFs) innervate distal dendrites, and both CF and PF inputs innervate a narrow intermediate domain. It is unclear how this segregated CF and PF innervation is established on PC dendrites. Through reconstruction of dendritic innervation by serial electron microscopy, we show that from postnatal day 9-15 in mice, both CF and PF innervation territories vigorously expand because of an enlargement of the region of overlapping innervation. From postnatal day 15 onwards, segregation of these territories occurs with robust shortening of the overlapping proximal region. Thus, innervation territories by the heterologous inputs are refined during the early postnatal period. Intriguingly, this transition is arrested in mutant mice lacking the type 1 metabotropic glutamate receptor (mGluR1) or protein kinase Cγ (PKCγ), resulting in the persistence of an abnormally expanded overlapping region. This arrested territory refinement is rescued by lentivirus-mediated expression of mGluR1α into mGluR1-deficient PCs. At the proximal dendrite of rescued PCs, PF synapses are eliminated and free spines emerge instead, whereas the number and density of CF synapses are unchanged. Because the mGluR1-PKCγ signaling pathway is also essential for the late-phase of CF synapse elimination, this signaling pathway promotes the two key features of excitatory synaptic wiring in PCs, namely CF monoinnervation by eliminating redundant CF synapses from the soma, and segregated territories of CF and PF innervation by eliminating competing PF synapses from proximal dendrites.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.