TrkB receptor signaling is required for establishment of GABAergic synapses in the cerebellum.
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.
Rico
Beatriz
B
Howard Hughes Medical Institute and Department of Physiology, University of California, San Francisco, California 94143, USA.
Xu
Baoji
B
Reichardt
Louis F
LF
D000818:Animals; D001369:Axons / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D050485:GABA Plasma Membrane Transport Proteins; D017930:Genes, Reporter; D005968:Glutamate Decarboxylase / Q000378:metabolism; D017403:In Situ Hybridization; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D027361:Organic Anion Transporters; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D011518:Proto-Oncogene Proteins; D014764:Viral Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins; D005680:gamma-Aminobutyric Acid; D020813:Receptor, trkB; C045073:Cre recombinase; D019426:Integrases; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2