PMID- 11850459 OWN - NLM STAT- MEDLINE DCOM- 20020226 LR - 20191023 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 22 IP - 4 DP - 2002 Feb 15 TI - Brain-derived neurotrophic factor modulates cerebellar plasticity and synaptic ultrastructure. PG - 1316-27 AB - Neurotrophins are key regulators of neuronal survival and function. Here we show that TrkB, the receptor for brain-derived neurotrophic factor (BDNF), is located at parallel fiber to Purkinje cell (PF/PC) synapses of the cerebellum. To determine the effects of TrkB receptor activation on synapse formation and function, we examined the parallel fiber to Purkinje cell synapses of mice with a targeted deletion of the BDNF gene. Although Purkinje cell dendrites are abnormal in BDNF -/- mice, PF/PC synapses are still able to form. Immunohistochemical analysis of mutant animals revealed the formation of numerous PF/PC synapses with the appropriate apposition of presynaptic and postsynaptic proteins. These synapses are functional, and no differences were detected in the waveform of evoked EPSCs, the amplitude of spontaneous mini-EPSCs, or the response to prolonged 10 Hz stimulus trains. However, paired-pulse facilitation, a form of short-term plasticity, is significantly decreased in BDNF -/- mice. Detailed ultrastructural analysis of the presynaptic terminals demonstrated that this change in synaptic function is accompanied by an increase in the total number of synaptic vesicles in mutant mice and a decrease in the proportion of vesicles that are docked. These data suggest that BDNF regulates both the mechanisms that underlie short-term synaptic plasticity and the steady-state relationship between different vesicle pools within the terminal. FAU - Carter, Alexandre R AU - Carter AR AD - Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Chen, Chinfei AU - Chen C FAU - Schwartz, Phillip M AU - Schwartz PM FAU - Segal, Rosalind A AU - Segal RA LA - eng GR - F31 LM000040/LM/NLM NIH HHS/United States GR - R01 NS037757/NS/NINDS NIH HHS/United States GR - NS37757/NS/NINDS NIH HHS/United States GR - 5F31LM00040-05/LM/NLM NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Calbindins) RN - 0 (Receptors, Glutamate) RN - 0 (S100 Calcium Binding Protein G) RN - 0 (glutamate receptor delta 2) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/deficiency/genetics/*metabolism/pharmacology MH - Calbindins MH - Cerebellum/cytology/*metabolism MH - Dendrites/ultrastructure MH - Electric Stimulation MH - Excitatory Postsynaptic Potentials/physiology MH - Gene Deletion MH - In Vitro Techniques MH - Mice MH - Mice, Knockout MH - Mice, Mutant Strains MH - Neuronal Plasticity/drug effects/*physiology MH - Patch-Clamp Techniques MH - Presynaptic Terminals/drug effects/metabolism/ultrastructure MH - Purkinje Cells/metabolism/ultrastructure MH - Receptor, trkB/metabolism MH - Receptors, Glutamate/metabolism MH - S100 Calcium Binding Protein G/metabolism MH - Synapses/drug effects/metabolism/*ultrastructure MH - Synaptic Transmission/physiology MH - Synaptic Vesicles/ultrastructure PMC - PMC6757568 EDAT- 2002/02/19 10:00 MHDA- 2002/02/28 10:01 PMCR- 2002/08/15 CRDT- 2002/02/19 10:00 PHST- 2002/02/19 10:00 [pubmed] PHST- 2002/02/28 10:01 [medline] PHST- 2002/02/19 10:00 [entrez] PHST- 2002/08/15 00:00 [pmc-release] AID - 22/4/1316 [pii] AID - 6081 [pii] AID - 10.1523/JNEUROSCI.22-04-01316.2002 [doi] PST - ppublish SO - J Neurosci. 2002 Feb 15;22(4):1316-27. doi: 10.1523/JNEUROSCI.22-04-01316.2002.