Repetitive firing deficits and reduced sodium current density in retinal ganglion cells developing in the absence of BDNF.
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.
Rothe
T
T
Developmental Physiology, Institute for Physiology, Humboldt University, Tucholskystr. 2, D-10117 Berlin.
Bähring
R
R
Carroll
P
P
Grantyn
R
R
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
D019208:Brain-Derived Neurotrophic Factor; D002121:Calcium Channel Blockers; D018118:Chloride Channels; D012964:Sodium