Repetitive firing deficits and reduced sodium current density in retinal ganglion cells developing in the absence of BDNF
✍ Scribed by Rothe, Thomas ;B�hring, Robert ;Carroll, Patrick ;Grantyn, Rosemarie
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 329 KB
- Volume
- 40
- Category
- Article
- ISSN
- 0022-3034
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✦ Synopsis
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.