The Function of Neural Activity in Developing Retina

PROJECT SUMMARY/ABSTRACT Spontaneous activity is a hallmark of developing neural systems. Prior to the maturation of vision, immature retinal neurons spontaneously generate correlated activity. This activity propagates in the form of waves of action potentials that sweep across the retinal ganglion cell layer. Retinal waves persist from embryonic day 16 through two weeks after birth, a developmental period when functional circuits within the retina are emerging and retinal projections to the brain are undergoing a tremendous amount of refinement. Here we explore three Aims regarding mechanisms underlying the function of retinal waves. In Aim 1, we focus on understanding the circuits that mediate embryonic retinal waves. At this age, the retina is comprised of retinal ganglion cells, a few amacrine cells, and an extensive neuroblastic layer in which the other cell types are differentiating. Despite the lack of mature circuit elements, retinal waves are robust. Here we test hypotheses regarding the relative role of gap junction coupling and synaptic transmission in mediating these waves. In Aim 2 we focus on second postnatal week when retinal waves exhibit a profound propagation bias. During this time period, the majority of waves travel in the nasal direction, a firing pattern which mimics optic flow induced by forward motion. Here we explore the hypothesis that this asymmetry in propagating activity is due to asymmetric connectivity between a GABAergic interneurons that are well integrated into wave generating circuits. Finally, in Aim 3 we investigate the role of retinal waves and visual stimulation of light-sensitive retinal ganglion cells in the release of dopamine in the developing retina. Though dopamine plays a key role in several developmental processes, what controls release is unknown. We will employ a novel imaging method that allows for measuring phasic dopamine release in parallel with calcium transients. Using this method, we will explore the relative role of retinal waves and light stimulation in mediating dopamine release during development.”