Translocation of a "winner" climbing fiber to the Purkinje cell dendrite and subsequent elimination of "losers" from the soma in developing cerebellum

Neuron. 2009 Jul 16;63(1):106-18. doi: 10.1016/j.neuron.2009.06.008.

Abstract

Functional neural circuits are formed by eliminating early-formed redundant synapses and strengthening necessary connections during development. In newborn mouse cerebellum, each Purkinje cell (PC) is innervated by multiple climbing fibers (CFs) with similar strengths. Subsequently, a single CF is selectively strengthened by postnatal day 7 (P7). We find that this competition among multiple CFs occurs on the soma before CFs form synapses along dendrites. Notably, in most PCs, the single CF that has been functionally strengthened (the "winner" CF) undergoes translocation to dendrites while keeping its synapses on the soma. Synapses of the weaker CFs (the "loser" CFs) remain around the soma and form "pericellular nests" with synapses of the winner CFs. Then most perisomatic synapses are eliminated nonselectively by P15. Thus, our results suggest that the selective translocation of the winner CF to dendrites in each PC determines the single CF that survives subsequent synapse elimination and persistently innervates the PC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aminobutyrates / pharmacology
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Biophysics
  • Biotin / analogs & derivatives
  • Biotin / metabolism
  • Calbindins
  • Cerebellum / cytology*
  • Cerebellum / growth & development*
  • Dendrites / drug effects
  • Dendrites / physiology*
  • Dextrans / metabolism
  • Electric Stimulation / methods
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Green Fluorescent Proteins / genetics
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal / methods
  • Nerve Fibers / physiology*
  • Nerve Net / physiology
  • Patch-Clamp Techniques / methods
  • Purkinje Cells / cytology*
  • Receptors, Serotonin / genetics
  • S100 Calcium Binding Protein G / metabolism
  • Synapses / drug effects
  • Synapses / physiology*
  • Time Factors
  • Vesicular Glutamate Transport Protein 2 / metabolism

Substances

  • Aminobutyrates
  • Calbindins
  • Dextrans
  • Receptors, Serotonin
  • S100 Calcium Binding Protein G
  • Slc17a6 protein, mouse
  • Vesicular Glutamate Transport Protein 2
  • biotinylated dextran amine
  • enhanced green fluorescent protein
  • serotonin 5 receptor
  • Green Fluorescent Proteins
  • Biotin
  • 2-amino-4-phosphonobutyric acid