Abstract
Neurotrophins are essential to the normal development and maintenance of the nervous system. Neurotrophin signaling is mediated by Trk family tyrosine kinases such as TrkA, TrkB and TrkC, as well as by the pan-neurotrophin receptor p75NTR. Here we have deleted the trkB gene in cerebellar precursors by Wnt1-driven Cre–mediated recombination to study the function of the TrkB in the cerebellum. Despite the absence of TrkB, the mature cerebellum of mutant mice appears similar to that of wild type, with all types of cell present in normal numbers and positions. Granule and Purkinje cell dendrites appear normal and the former have typical numbers of excitatory synapses. By contrast, inhibitory interneurons are strongly affected: although present in normal numbers, they express reduced amounts of GABAergic markers and develop reduced numbers of GABAergic boutons and synaptic specializations. Thus, TrkB is essential to the development of GABAergic neurons and regulates synapse formation in addition to its role in the development of axon terminals.
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Acknowledgements
We thank A. P. McMahon and P. Soriano for the Wnt1Cre and R26R transgenic mice; O. Marín, M. Stryker, S. Bamji, L. Elia, T. Elul, U. Fünfschilling and J. Zhu for comments on the manuscript; S. Huling, and I. Hsie for assistance with electron microscopy; N. Brecha for the antibody against GAT-1; and A. Stephenson for the antibody against the α6 subunit of the GABAA receptor. This work was supported by a grant from the USPH and by the HHMI. B.R. was supported by a postdoctoral fellowship from the Ministerio de Educación, Spain. L.F.R. is an Investigator of the HHMI.
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Rico, B., Xu, B. & Reichardt, L. TrkB receptor signaling is required for establishment of GABAergic synapses in the cerebellum. Nat Neurosci 5, 225–233 (2002). https://doi.org/10.1038/nn808
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DOI: https://doi.org/10.1038/nn808
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