title: Repetitive firing deficits and reduced sodium current density in retinal ganglion cells developing in the absence of BDNF.
abstract: 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.
authors.affiliation: Developmental Physiology, Institute for Physiology, Humboldt University, Tucholskystr. 2, D-10117 Berlin.
authors.forename: T
authors.initials: T
authors.lastname: Rothe
authors.forename: R
authors.initials: R
authors.lastname: Bähring
authors.forename: P
authors.initials: P
authors.lastname: Carroll
authors.forename: R
authors.initials: R
authors.lastname: Grantyn
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency* / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D004553:Electric Conductivity; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002121:Calcium Channel Blockers; D018118:Chloride Channels; D012964:Sodium