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
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.