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The Journal of Neuroscience, May 15, 1998, 18(10):3563-3573
Granule Neuron Regulation of Purkinje Cell Development: Striking a Balance Between Neurotrophin and Glutamate Signaling
Mary E. Morrison and Carol A. Mason Departments of Pathology, and Anatomy and Cell Biology, Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, New York 10032
Granule neurons, presynaptic afferents of Purkinje cells, are potent regulators of Purkinje cell development. Purified Purkinje cells survive and differentiate poorly, whereas coculture with granule neurons enhances their survival and dendritic development. Here we investigate the role of neurotrophins in granule-Purkinje cell interactions. BDNF or NT-4 improves, but NT-3 or CNTF reduces, survival of isolated Purkinje cells. When granule neurons are present, however, BDNF or NT-4 treatment leads to Purkinje cell loss. This decrease is overcome by anti-BDNF or TrkB-IgG-blocking reagents or by CNQX, a non-NMDA glutamate receptor antagonist. Furthermore, BDNF increases the spine density on the surviving Purkinje cells. These results suggest that Purkinje cell survival and differentiation are context-dependent and require a balance between neurotrophin- and activity-dependent signaling.
Key words: Purkinje cell; granule cell; cerebellum; neurotrophins; BDNF; CNQX; spines
Copyright © 1998 Society for Neuroscience 0270-6474/98/18103563-11$05.00/0
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