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

Although correlated neural activity is a hallmark of many regions of the de veloping nervous system, the neural events underlying its propagation remai n largely unknown. In the developing vertebrate retina, waves of spontaneou s, correlated neural activity sweep across the ganglion cell layer. Here, w e demonstrate that L-type Ca2+ channel agonists induce large, frequent, rap idly propagating waves of neural activity in the developing retina. In cont rast to retinal waves that have been described previously, these L-type Ca2 + channel agonist-potentiated waves propagate independent of fast synaptic transmission. Bath application of nicotinic acetylcholine, AMPA, NMDA, glyc ine, and GABAA receptor antagonists does not alter the velocity, frequency, or size of the potentiated waves. Additionally, these antagonists do not a lter the frequency or magnitude of spontaneous depolarizations that are rec orded in individual retinal ganglion cells. Like normal retinal waves, howe ver, the area over which the potentiated waves propagate is reduced dramati cally by 18 alpha -glycyrrhetinic acid, a blocker of gap junctions. Additio nally, like normal retinal waves, L-type Ca2+ channel agonist-potentiated w aves are abolished by adenosine deaminase, which degrades extracellular ade nosine, and by aminophylline, a general adenosine receptor antagonist, indi cating that they are dependent on adenosine-mediated signaling. Our study i ndicates that although the precise spatiotemporal properties of retinal wav es are shaped by local synaptic inputs, activity may be propagated through the developing mammalian retina by nonsynaptic pathways.