Prior to phototransduction, spontaneous activity in the developing mammalian retina is necessary for normal development of circuits throughout the visual system. Our primary research interests are to investigate the mechanisms and function underlying spontaneous activity in the developing retina. Immature retinal neurons spontaneously generate correlated activity in the form of waves of action potentials that sweep across the retinal ganglion cell layer. """"""""Retinal waves"""""""" are modulated by synaptic transmission from interneurons, but the mechanism of inter-cellular coupling that underlies their propagation is not understood. We investigated wave propagation by using a combination of electrophysiology and imaging. Voltage-gated Ca2+ channel agonists dramatically altered the propagation of neural activity across the developing retina by increasing the velocity, area, and frequency of retinal waves. Remarkably, waves persisted in the presence of neurotransmitter antagonists that block retinal waves under control conditions. Our results indicate that neural activity can propagate in the absence of known forms of fast synaptic transmission. We are currently investigating whether these waves are propagated via gap junctions between retinal neurons or extracellular diffusion of an excitatory substance. We also conducted experiments to study the role of retinal waves in the development of circuits within the retina. The synaptic layer of the retina is organized into distinct strata where different classes of neurons make their synaptic connections in spatially segregated bands. We used immunohistochemistry and neuronal tracers in transgenic mice lacking the b2 subunit of the nicotinic acetylcholine receptor (nAChR), known to be required for wave propagation. These mice exhibit greatly reduced retinal wave activity during the first postnatal week, but display normal levels of activity in the second postnatal week. In b2-/- mice, the development and morphology of a variety of neuronal cell types, including the axons of cholinergic neurons and the gross segregation of retinal ganglion cell (RGC) dendrites were normal. However, the refinement of individual RGC dendrites is delayed. These results indicate that retinal waves mediated by nAChRs are involved in, but not required for, the development of neural circuits that define the synaptic layers of the retina.
