PROJECT SUMMARY Corticogeniculate (CG) neurons that connect primary visual cortex (V1) to the lateral geniculate nucleus of the thalamus (LGN) make up the first feedback circuit in the visual hierarchy. Although CG synapses onto LGN neurons outnumber synapses coming from the retina, LGN receptive fields resemble those of their feedforward retinal inputs and not their cortical inputs. The subtle, modulatory role of CG feedback has made understanding its structure and function an enduring problem in visual neuroscience. This project proposes two sets of experiments to establish the rules of connectivity between CG and LGN neurons and to examine the influence of CG neurons on LGN ensemble activity in ferrets. Several studies in carnivore and primate have demonstrated that CG feedback neurons are morphologically and physiologically heterogeneous, providing a substrate for parallel streams of feedback that correspond with the feedforward parallel streams in the retino-geniculo-cortical pathways. However, whether the functional connections between CG and LGN neurons are stream-specific or mixed is not known. Aim 1 will investigate how CG neurons are functionally connected to LGN neurons. Simultaneous recordings from functionally connected CG and LGN neurons in ferrets and a multidimensional analysis of tuning properties will be used to rigorously classify these neurons and establish whether functional connections are made preferentially between CG and LGN neurons with similar tuning. Aim 2 will examine the composition of correlated LGN ensembles and how CG feedback influences the visual response dynamics and ensemble tuning of small populations of LGN neurons. Previous work has established that CG feedback regulates the timing, precision, and synchrony of LGN responses. We hypothesize that the effects of feedback will depend on 1.) whether CG-LGN connectivity is feature-specific or mixed, and 2.) the cell-type composition of LGN ensembles. Aim 2 will first determine whether ensembles of correlated LGN neurons are feature-specific. Then, virus-mediated gene delivery targeting CG neurons will be used to optogenetically activate CG feedback while recording from ensembles of LGN neurons. Together these experiments will advance knowledge of early visual circuits by clarifying the connectivity between CG and LGN neurons and establishing the effect of CG feedback on LGN ensemble activity. The training during this project will focus on increasing proficiency in computational analyses, as well as improving experimental techniques and professional development for a career as a future independent investigator, under the guidance of Dr. Farran Briggs, a leading researcher on corticogeniculate feedback, and Dr. Krishnan Padmanabhan, an expert in computational systems neuroscience. This research will be conducted at the University of Rochester, an institution with a strong Neuroscience Graduate Program and a renowned Center for Visual Science, which will provide excellent opportunities for academic and professional growth.