Granule neuron regulation of Purkinje cell development: striking a balance between neurotrophin and glutamate signaling.
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.
Morrison
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ME
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, USA.
Mason
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CA
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000633:toxicity; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D020933:Neurotrophin 3; D011247:Pregnancy; D011689:Purkinje Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D001798:Blood Proteins; D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D016895:Culture Media, Serum-Free; D018691:Excitatory Amino Acid Antagonists; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D020933:Neurotrophin 3; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C073922:neurotrophin 4