Brain-derived neurotrophic factor modulates cerebellar plasticity and synaptic ultrastructure.
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.
Carter
Alexandre R
AR
Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Chen
Chinfei
C
Schwartz
Phillip M
PM
Segal
Rosalind A
RA
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D064026:Calbindins; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D003712:Dendrites / Q000648:ultrastructure; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017353:Gene Deletion; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011689:Purkinje Cells / Q000378:metabolism / Q000648:ultrastructure; D020813:Receptor, trkB / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000648:ultrastructure
D019208:Brain-Derived Neurotrophic Factor; D064026:Calbindins; D017470:Receptors, Glutamate; D064030:S100 Calcium Binding Protein G; C107913:glutamate receptor delta 2; D020813:Receptor, trkB