Functional circuitry and computation of the visual thalamus

PROJECT SUMMARY/ABSTRACT The dorsal lateral geniculate nucleus (dLGN) of the thalamus routes visual signals from the eye to the visual cortex and provides critical support for conscious visual sensation. Rather than being a simple relay station, a growing body of evidence is revealing that the mouse dLGN plays an active role in shaping visual information flow to the cortex by selectively converging and integrating diverse streams of inputs. Studies of retinal inputs to the dLGN have provided rich knowledge about the organization and development of neural circuits for mammalian species. However, much less is known about the non-retinal inputs although they contribute to ~90% of total inputs to the dLGN. How the visual and behavioral state information conveyed by non-retinal inputs combines with information from the retina to impact thalamic visual processing remains a topic of great experimental and theoretical interest. Direct functional characterization of inputs to the dLGN in awake behaving animals has been hindered by the difficulty in performing high-resolution recording of subcortical brain regions. To address this challenge, we established a chronic, high-resolution, deep-brain two-photon calcium imaging platform to simultaneously measure visual responses in hundreds of retinal axonal boutons. Here, we have further expanded our imaging capacity to simultaneously record signals from calcium indicators of two different colors that are expressed in retinal and non-retinal inputs respectively. With these innovations, we will determine how the diverse inputs from the midbrain superior colliculus coordinate with retinal inputs at multiple levels to reinforce or broaden channels of visual information in the dLGN. The highly conserved colliculogeniculate axons possess several synaptic properties that resemble those of retinogeniculate axons, including comingling axonal boutons on the proximal dendrites of dLGN neurons and providing strong synaptic inputs that can elicit neural firing in target neurons. However, it remains unclear how the collicular inputs combine with retinal inputs and contribute to visual responses of dLGN neurons. In Aim 1, we will determine the functional and spatial relationships between retinal and collicular inputs to the dLGN. In Aim 2, we will reveal the modulation of colliculogeniculate inputs by behavioral states. In Aim 3, we will determine the contribution of collicular inputs to visual responses of dLGN neurons. These experiments will reveal rules for functional convergence between retinal and collicular inputs and demonstrate how they act in concert or in competition to sculpt thalamic visual computation. Our findings will also contribute to the understanding of how afferent visual signals are transformed into visual feature selectivity in the dLGN and how behavioral states impact this process, providing the foundation for the understanding and treatment of neurological disorders involving improper neural circuit connectivity and signal integration.