Potentiation of L-type calcium channels reveals nonsynaptic mechanisms that correlate spontaneous activity in the developing mammalian retina

J Neurosci. 2001 Nov 1;21(21):8514-22. doi: 10.1523/JNEUROSCI.21-21-08514.2001.

Abstract

Although correlated neural activity is a hallmark of many regions of the developing nervous system, the neural events underlying its propagation remain largely unknown. In the developing vertebrate retina, waves of spontaneous, correlated neural activity sweep across the ganglion cell layer. Here, we demonstrate that L-type Ca(2+) channel agonists induce large, frequent, rapidly propagating waves of neural activity in the developing retina. In contrast to retinal waves that have been described previously, these L-type Ca(2+) channel agonist-potentiated waves propagate independent of fast synaptic transmission. Bath application of nicotinic acetylcholine, AMPA, NMDA, glycine, and GABA(A) receptor antagonists does not alter the velocity, frequency, or size of the potentiated waves. Additionally, these antagonists do not alter the frequency or magnitude of spontaneous depolarizations that are recorded in individual retinal ganglion cells. Like normal retinal waves, however, the area over which the potentiated waves propagate is reduced dramatically by 18alpha-glycyrrhetinic acid, a blocker of gap junctions. Additionally, like normal retinal waves, L-type Ca(2+) channel agonist-potentiated waves are abolished by adenosine deaminase, which degrades extracellular adenosine, and by aminophylline, a general adenosine receptor antagonist, indicating that they are dependent on adenosine-mediated signaling. Our study indicates that although the precise spatiotemporal properties of retinal waves are shaped by local synaptic inputs, activity may be propagated through the developing mammalian retina by nonsynaptic pathways.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Animals, Newborn
  • Calcium Channel Agonists / pharmacology
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / metabolism*
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Cell Communication / drug effects
  • Cell Communication / physiology*
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology
  • Fluorescent Dyes
  • GABA Antagonists / pharmacology
  • GABA-A Receptor Antagonists
  • Gap Junctions / drug effects
  • Gap Junctions / metabolism*
  • Glycine Agents / pharmacology
  • Glycyrrhetinic Acid / pharmacology
  • In Vitro Techniques
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Retina / cytology
  • Retina / growth & development*
  • Retina / metabolism*
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Calcium Channel Agonists
  • Calcium Channels, L-Type
  • Excitatory Amino Acid Antagonists
  • Fluorescent Dyes
  • GABA Antagonists
  • GABA-A Receptor Antagonists
  • Glycine Agents
  • Glycyrrhetinic Acid