Repetitive firing deficits and reduced sodium current density in retinal ganglion cells developing in the absence of BDNF

J Neurobiol. 1999 Sep 5;40(3):407-19. doi: 10.1002/(sici)1097-4695(19990905)40:3<407::aid-neu12>;2-t.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain-Derived Neurotrophic Factor / deficiency*
  • Brain-Derived Neurotrophic Factor / drug effects
  • Calcium Channel Blockers / pharmacology
  • Cell Count / drug effects
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Chloride Channels / drug effects
  • Chloride Channels / metabolism
  • Electric Conductivity
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Ion Transport / drug effects
  • Ion Transport / physiology
  • Mice
  • Mice, Transgenic
  • Nerve Fibers, Myelinated / drug effects
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / physiology*
  • Patch-Clamp Techniques
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism*
  • Sodium / metabolism*
  • Synapses / drug effects
  • Synapses / physiology


  • Brain-Derived Neurotrophic Factor
  • Calcium Channel Blockers
  • Chloride Channels
  • Sodium