In the visual system, neighboring retinal ganglion cells (RGCs) fire in correlated bursts of spikes, resulting in propagating waves, which are considered crucial to the formation of visual system circuitry. The existence and properties of stage III waves, which are thought present from P10 until around the time of eye opening, are as yet undetermined in vivo. In my research plan, I propose to comprehensively examine the properties of stage III waves in the retina and developing mammalian visual system, and test the hypothesis that stage III waves have distinct properties that are uniquely suited to drive the emergence of orientation-selective receptive fields prior to the time of eye opening. My preliminary data suggests that stage III retinal waves are more frequent and smaller than stage II waves, however they do propagate in a wave like fashion, which was not previously appreciated from in vitro experiments. Using in vivo imaging techniques previously established in the lab, we will quantitatively characterize the properties of retinal waves by measuring retina ganglion cell axon terminal activity in the superior colliculus in vivo during the second postnatal week. We propose to examine and quantitatively compare the properties of stage III `glutamate' waves in neurons of the LGN, superior colliculus and visual cortex using conditional expression of GcAMP6 and Ca2+ imaging in vivo. We will also examine the effects of pharmacological manipulations in the eye on the propagation of retinal waves to higher order visual circuits. Finally, in order to test role of separately recruited ON-OFF waves, I will chronically manipulate the firing of ON and OFF RGCs through the daily application of inhibitory antagonists to the retina. These experiments will establish whether stage III waves are present and capable of patterning circuits throughout the visual system in vivo, and whether they are responsible for fundamental features of V1 neuron receptive fields.
In the mammalian visual system, correlated waves of spontaneous activity is instructive for the wiring of functional connections during perinatal development. My proposed studies will examine the properties of stage III `glutamate' waves in vivo throughout the visual system, and examine whether and how the unique spatiotemporal properties of stage III waves participate in visual circuit development, particularly in the formation of orientation specific receptive fields in the visual cortex. This work could lead to ne therapeutic strategies to combat and repair abnormalities in the developing visual system.
| Babola, Travis A; Li, Sally; Gribizis, Alexandra et al. (2018) Homeostatic Control of Spontaneous Activity in the Developing Auditory System. Neuron 99:511-524.e5 |
| Thompson, Andrew; Gribizis, Alexandra; Chen, Chinfei et al. (2017) Activity-dependent development of visual receptive fields. Curr Opin Neurobiol 42:136-143 |
