Functional maturation in the retina, thalamus and cortex

Harvard University (Medical School), Boston MA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): In the adult, synaptic connections from retina to thalamus and from thalamus to primary visual cortex are distinguished by their great specificity. Past work has shown that these connections are found only if the receptive field of the presynaptic neuron is well matched to the receptive field of its target. In the pathway from retina to thalamus (the lateral geniculate nucleus, or LGN), this relationship is straightforward. An LGN neuron receives only one or two strong inputs and the receptive-field centers of pre- and postsynaptic neurons are very similar. In the thalamocortical pathway, the relationship is more complicated. There is a large pool of potential thalamic inputs to any layer 4 cortical neuron, but only 1/3 of these afferents are functionally appropriate; it is this subset that makes functional connections. [unreadable] [unreadable] We will study animals in the weeks after eye opening, during which the specific connections seen in the adult are formed. Retinothalamic connections at eye opening are highly convergent. Over the next few weeks of development, the connections are pared down to the one-to-one (or several-to-one) connections seen in the adult. Much less is known of the fine-scale refinement in the thalamolocortical system. It is clear that refinement is proceeding simultaneously at two levels: between retina and LGN, and between LGN and visual cortex. Surprisingly little is known of the relative rates of this two-level process, or of how the process of maturation at one level affects the next. [unreadable] [unreadable] We propose to study three aspects of visual development in the weeks after eye opening. (A) We will compare receptive fields between levels (retina and LGN, or LGN and cortex) to assess directly the relative rates of functional maturation. (B) We will study correlations among nearby neurons, both in the retina and in the LGN. It is widely accepted that correlated activity among presynaptic neurons drives the refinement of their connections onto specific targets, but very little is known about these correlations in the weeks after eye opening. (C) Finally, we will examine how correlations in the retina caused by visual stimuli can instructively affect retinogeniculate connections: specifically how visual experience can modify geniculate receptive fields over the time-course of minutes to hours. This basic research will further our knowledge of normal development in the visual system and potentially help us understand disorders of neural development.