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TrkB (tropomyosin-related kinase B) controls the assembly and maintenance of GABAergic synapses in the cerebellar cortex.

Inhibitory interneurons play a critical role in coordinating the activity of neural circuits. To explore the mechanisms that direct the organization of inhibitory circuits, we analyzed the involvement of tropomyosin-related kinase B (TrkB) in the assembly and maintenance of GABAergic inhibitory synapses between Golgi and granule cells in the mouse cerebellar cortex. We show that TrkB acts directly within each cell-type to regulate synaptic differentiation. TrkB is required not only for assembly, but also maintenance of these synapses and acts, primarily, by regulating the localization of synaptic constituents. Postsynaptically, TrkB controls the localization of a scaffolding protein, gephyrin, but acts at a step subsequent to the localization of a cell adhesion molecule, Neuroligin-2. Importantly, TrkB is required for the localization of an Ig superfamily cell adhesion molecule, Contactin-1, in Golgi and granule cells and the absence of Contactin-1 also results in deficits in inhibitory synaptic development. Thus, our findings demonstrate that TrkB controls the assembly and maintenance of GABAergic synapses and suggest that TrkB functions, in part, through promoting synaptic adhesion.

Pubmed ID: 21414899

Authors

  • Chen AI
  • Nguyen CN
  • Copenhagen DR
  • Badurek S
  • Minichiello L
  • Ranscht B
  • Reichardt LF

Journal

The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

February 23, 2011

Associated Grants

  • Agency: NEI NIH HHS, Id: EY01869
  • Agency: NINDS NIH HHS, Id: NS038297
  • Agency: NINDS NIH HHS, Id: NS16033
  • Agency: NINDS NIH HHS, Id: P01 NS016033
  • Agency: NINDS NIH HHS, Id: P01 NS016033-26
  • Agency: NEI NIH HHS, Id: R01 EY001869
  • Agency: NEI NIH HHS, Id: R01 EY001869-33
  • Agency: NINDS NIH HHS, Id: R01 NS038297
  • Agency: NINDS NIH HHS, Id: R01 NS038297-04
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Cell Adhesion
  • Cell Differentiation
  • Cerebellar Cortex
  • Interneurons
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Receptor, trkB
  • Synapses
  • Synaptic Transmission
  • Tropomyosin
  • gamma-Aminobutyric Acid