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Publication : Repetitive firing deficits and reduced sodium current density in retinal ganglion cells developing in the absence of BDNF.

First Author  Rothe T Year  1999
Journal  J Neurobiol Volume  40
Issue  3 Pages  407-19
PubMed ID  10440740 Mgi Jnum  J:57427
Mgi Id  MGI:1344570 Doi  10.1002/(sici)1097-4695(19990905)40:3<407::aid-neu12>3.0.co;2-t
Citation  Rothe T, et al. (1999) Repetitive firing deficits and reduced sodium current density in retinal ganglion cells developing in the absence of BDNF. J Neurobiol 40(3):407-19
abstractText  Previous work by Cellerino et al. has shown that chronic absence of brain-derived neurotrophic factor (BDNF) resulted in hypomyelination of the optic nerve. Since myelination is influenced by neuronal activity, it is possible that a deficiency in BDNF during early development could alter the firing properties of retinal neurons. To test this hypothesis, patch-clamp recordings were performed in retinal whole mounts from BDNF-deficient (bdnf-/-), heterozygote (bdnf+/-) or wild-type control mice (bdnf+/+). Ganglion cell layer neurons (RGNs) were tested at different age [postnatal day (P)1-11] for their ability to encode graded depolarization with variable action potential frequency. At all developmental ages examined, RGNs exhibiting frequency coding were less frequently encountered in bdnf-/- than in bdnf+/+ mice. At P1, none of the RGNs from bdnf-/- mice displayed repetitive firing compared to 50% in bdnf+/+ mice, and by P7-11, only 50% of bdnf-/- RGNs exhibited repetitive firing compared to 100% in bdnf+/+ mice. Moreover, in bdnf-/- RGNs repetitive discharge was characterized by a reduced frequency increment per current change. Acquisition of repetitive firing was paralleled by a decrease in input resistance and a steep increase of sodium current density. In bdnf-/- mice, the onset of this increase occurred at later stages of development than in wild-type controls (bdnf-/-: P6-11; bdnf+/+: P2-6). The discharge pattern of P7-11 bdnf-/- RGNs resembled that of RGNs in neonatal wild-type mice and was mimicked by acute application of a Ca(2+) channel blocker. We conclude that BDNF plays an important role in the ontogeny of repetitive firing of RGNs. Copyright 1999 John Wiley & Sons, Inc.
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