PMID- 10440740 OWN - NLM STAT- MEDLINE DCOM- 19991220 LR - 20191103 IS - 0022-3034 (Print) IS - 0022-3034 (Linking) VI - 40 IP - 3 DP - 1999 Sep 5 TI - Repetitive firing deficits and reduced sodium current density in retinal ganglion cells developing in the absence of BDNF. PG - 407-19 AB - 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. CI - Copyright 1999 John Wiley & Sons, Inc. FAU - Rothe, T AU - Rothe T AD - Developmental Physiology, Institute for Physiology, Humboldt University, Tucholskystr. 2, D-10117 Berlin. FAU - Bahring, R AU - Bahring R FAU - Carroll, P AU - Carroll P FAU - Grantyn, R AU - Grantyn R LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurobiol JT - Journal of neurobiology JID - 0213640 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Calcium Channel Blockers) RN - 0 (Chloride Channels) RN - 9NEZ333N27 (Sodium) SB - IM MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/*deficiency/drug effects MH - Calcium Channel Blockers/pharmacology MH - Cell Count/drug effects MH - Cell Differentiation/drug effects/physiology MH - Cell Membrane/drug effects/metabolism MH - Chloride Channels/drug effects/metabolism MH - Electric Conductivity MH - Excitatory Postsynaptic Potentials/drug effects/physiology MH - Ion Transport/drug effects/physiology MH - Mice MH - Mice, Transgenic MH - Nerve Fibers, Myelinated/drug effects MH - Neurons, Afferent/drug effects/*physiology MH - Patch-Clamp Techniques MH - Retinal Ganglion Cells/drug effects/*metabolism MH - Sodium/*metabolism MH - Synapses/drug effects/physiology EDAT- 1999/08/10 00:00 MHDA- 1999/08/10 00:01 CRDT- 1999/08/10 00:00 PHST- 1999/08/10 00:00 [pubmed] PHST- 1999/08/10 00:01 [medline] PHST- 1999/08/10 00:00 [entrez] AID - 10.1002/(SICI)1097-4695(19990905)40:3<407::AID-NEU12>3.0.CO;2-T [pii] AID - 10.1002/(sici)1097-4695(19990905)40:3<407::aid-neu12>3.0.co;2-t [doi] PST - ppublish SO - J Neurobiol. 1999 Sep 5;40(3):407-19. doi: 10.1002/(sici)1097-4695(19990905)40:3<407::aid-neu12>3.0.co;2-t.