Requirement of TrkB for synapse elimination in developing cerebellar Purkinje cells.
The receptor tyrosine kinase TrkB and its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5), are critically important for growth, survival and activity-dependent synaptic strengthening in the central nervous system. These TrkB-mediated actions occur in a highly cell-type specific manner. Here we report that cerebellar Purkinje cells, which are richly endowed with TrkB receptors, develop a normal morphology in trkB-deficient mice. Thus, in contrast to other types of neurons, Purkinje cells do not need TrkB for dendritic growth and spine formation. Instead, we find a moderate delay in the maturation of GABAergic synapses and, more importantly, an abnormal multiple climbing fiber innervation in Purkinje cells in trkB-deficient mice. Thus, our results demonstrate an involvement of TrkB receptors in synapse elimination and reveal a new role for receptor tyrosine kinases in the brain.
Bosman
Laurens W J
LW
Institut für Neurowissenschaften, Technische Universität München, Biedersteiner Strasse 29, 80802, München, Germany.
Hartmann
Jana
J
Barski
Jaroslaw J
JJ
Lepier
Alexandra
A
Noll-Hussong
Michael
M
Reichardt
Louis F
LF
Konnerth
Arthur
A
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D048430:Cell Shape / Q000502:physiology; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D049229:Dendritic Spines / Q000502:physiology; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D011689:Purkinje Cells / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D005680:gamma-Aminobutyric Acid; D020813:Receptor, trkB