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The Journal of Neuroscience, February 15, 2002, 22(4):1316-1327

Brain-Derived Neurotrophic Factor Modulates Cerebellar Plasticity and Synaptic Ultrastructure

Alexandre R. Carter¹, Chinfei Chen², Phillip M. Schwartz¹, and Rosalind A. Segal¹

¹ Department of Pediatric Oncology, Dana Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, and ² Division of Neuroscience, Department of Neurology, Children's Hospital, Boston, Massachusetts 02115

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.

Key words: neurotrophin; BDNF; Trk receptor; cerebellum; facilitation; ultrastructure; presynaptic plasticity

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Copyright © 2002 Society for Neuroscience  0270-6474/02/2241316-12$05.00/0

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