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

Citation
T. Rothe et al., Repetitive firing deficits and reduced sodium current density in retinal ganglion cells developing in the absence of BDNF, J NEUROBIOL, 40(3), 1999, pp. 407-419
Citations number
47
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROBIOLOGY
ISSN journal
00223034 → ACNP
Volume
40
Issue
3
Year of publication
1999
Pages
407 - 419
Database
ISI
SICI code
0022-3034(19990905)40:3<407:RFDARS>2.0.ZU;2-A
Abstract
Previous work by Cellerino et al, has shown that chronic absence of brain-d erived 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 recordi ngs were performed in retinal whole mounts from BDNF-deficient (bdnf(-/-)), heterozygote (bdnf(+/-)) or wild-type control mice (bdnf(+/+)). Ganglion c ell layer neurons (RGNs) were tested at different age [postnatal day (P)1-1 1] for their ability to encode graded depolarization with variable action p otential frequency. At all developmental ages examined, RGNs exhibiting fre quency coding were less frequently encountered in bdnf(-/-) than in bdnf(+/ +) mice, At P1, none of the RGNs from bdnf(-/-) mice displayed repetitive f iring compared to 50% in bdnf(+/+) mice, and by P7-11, only 50% of bdnf(-/- ) RGNs exhibited repetitive firing compared to 100% in bdnf(+/+) mice. More over, in bdnf(-/-) RGNs repetitive discharge was characterized by a reduced frequency increment per current change, Acquisition of repetitive firing w as paralleled by a decrease in input resistance and a steep increase of sod ium current density. In bdnf(-/-) mice, the onset of this increase occurred at later stages of development than in wild-type controls (bdnf(-/-): P6-1 1; bdnf(+/+): P2-6). The discharge pattern of P7-11 bdnf(-/-) RGNs resemble d that of RGNs in neonatal wild-type mice and was mimicked by acute applica tion of a Ca2+ channel blocker. We conclude that BDNF plays an important ro le in the ontogeny of repetitive firing of RGNs, (C) 1999 John Wiley & Sons , Inc. J Neurobiol 40: 407-419, 1999.