Mechanisms underlying spontaneous glutamatergic activity in developing mouse retina
Throughout the developing nervous system, spontaneous oscillatory patterns of activity have been observed. The developing murine retina is no exception, where spontaneous activity manifests as spatially correlated waves of depolarizations. These retinal waves propagate between neighboring neurons within retinal layers during the two postnatal weeks just prior to eye-opening and development of the light response. Waves are necessary for the normal patterning of connections of the retinal projections to their primary targets in the brain, indicating they contribute to a general self-organizing principal of neural development.
There are three distinct circuits that mediate these waves at different developmental stages: gap junction mediated waves that occur around birth, acetylcholine-receptor mediated that occur during the first postnatal week, and glutamate-receptor mediated that occur between postnatal day 10 (P10) and P13. At this age, retinal circuitry appears adult-like such that excitatory synapses connect neurons across layers but inhibitory synapses connect neurons within layers. Thus it remains a mystery as to how depolarization propagates between neighboring within-layer neurons during waves.
This dissertation addresses the cellular and synaptic basis underlying the initiation and propagation of glutamatergic retinal waves. Using a combination of multielectrode array recording and two-photon calcium imaging, I identified a role for electrical coupling, diffuse release of glutamate, and inhibitory circuits in the retinal wave generation. In addition, I studied the role of endogenous copper in modulating retinal waves. This research represents a near-complete description of the intraretinal circuits that underlie the spatial and temporal properties of glutamatergic retinal waves.