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NEUROSCIENCE |
1 Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756, USA
TrkB, the cognate receptor for brain-derived neurotrophic factor and neurotrophin-4, has been implicated in regulating synapse formation in the central nervous system. Here we asked whether TrkB plays a role in the maturation of the climbing fibrePurkinje cell (CFPC) synapse. In rodent cerebellum, Purkinje cells are initially innervated by multiple climbing fibres that are subsequently culled to assume the mature mono-innervated state, and whose contacts translocate from the soma to the dendrites. By employing transgenic mice hypomorphic or null for TrkB expression, our results indicated that perturbation of TrkB in the immature cerebellum resulted in ataxia, that Purkinje cells remained multiply innervated by climbing fibres beyond the normal developmental time frame, and that synaptic transmission at the parallel fibrePurkinje cell synapse remained functionally unaltered. Mechanistically, we present evidence that attributes the persistence of multiple climbing fibre innervation to an obscured discrimination of relative strengths among competing climbing fibres. Soma-to-dendrite translocation of climbing fibre terminals was unaffected. Thus, TrkB regulates pruning but not translocation of nascent CFPC synaptic contacts.
(Received 28 March 2007;
accepted after revision 20 April 2007;
first published online 26 April 2007)
Corresponding author Hermes H. Yeh: Department of Physiology, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA. Email: hermes.yeh{at}dartmouth.edu
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