The neuronal image of the visual scene that is processed by the retina is the result of a complex interplay between excitation and inhibition and is conducted to the brain by retinal ganglion cell (RGC) spike activity. In early life, this visual-evoked activity affects the synaptic integration and visual signal processing in lateral geniculate nucleus and visual cortex. Little is known about whether retinal neuronal connections and synaptic activities are also regulated by visual experience. One of the goals in this proposed study is to identify and quantify the synaptic inputs to RGCs and characterize the roles of development on the regulation of synaptic activity of these cells. Toward this end the spontaneous and light-evoked excitatory and inhibitory synaptic inputs of RGCs will be studied using patch electrode recording techniques from retinal slice preparation. The developmental profiles of excitatory and inhibitory synaptic activities in mouse RGCs will be determined. In addition, the roles of interaction of excitatory and inhibitory neuron transmitters on the developmental regulation of RGC synaptic activity will be examined in wild type mice and two types of transgenic mice (GAD65-/- and mGluR6-/-). Another primary goal is to determine the roles of visual experience on the development of RGC synaptic activity and to understand the mechanisms of experience-dependent synaptic plasticity in the retina. The synaptic inputs of RGCs from light-deprived and normally reared mice will be studied. The time course, critical period and reversibility of light deprivation-induced effects of RGC synaptic activity will be characterized. The roles of interactions between visual experience and neurotransmitters on the developmental regulation of synaptic will also be determined by using the transgenic mice in which the release of excitatory and inhibitory neurotransmitters is altered. The results of these studies have important implications in how we view pathologies that affect vision during infancy and childhood. They also provide insights to how neurotransmitter-related therapeutic drugs could affect normal development of the human visual system.
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