Dynamics of retinal waves are controlled by cyclic AMP

Waves of spontaneous activity sweep across the developing mammalian retina and influence the pattern of central connections made by ganglion cell axon s. These waves are driven by synaptic input from amacrine cells. We show th at cholinergic synaptic transmission during waves is not blocked by TTX, in dicating that release from starburst amacrine cells is independent of sodiu m action potentials. The spatiotemporal properties of the waves are regulat ed by endogenous release of adenosine, which sets intracellular cAMP levels through activation of A2 receptors present on developing amacrine and gang lion cells. Increasing cAMP levels increase the size, speed, and frequency of the waves. Conversely, inhibiting adenylate cyclase or PKA prevents wave activity. Together, these results imply a novel mechanism in which levels of cAMP within an immature retinal circuit regulate the precise spatial and temporal patterns of spontaneous neural activity.