Functional identification of primate lateral geniculate nucleus projections to visual cortex using optogenetics and electrical stimulation

Optogenetics and electrical stimulation are routinely used to assess neuronal connectivity. However cell-specific approaches, especially in primates, are still very limited. Here we compare the capacities of optogenetics and electrical stimulation to isolate the specific pathways from the lateral geniculate nucleus (LGN) to primary visual cortex (V1) in the macaque visual system. The organization of LGN into three anatomically separate and neurochemically distinct cell projection systems with virtually no cross-talk provides unique conditions to test for cell-specific targeting by electrical and optogenetic stimulation techniques. For the optogenetics experiments, we injected AAV5-CamKIIα-ChR2-eYFP into the LGN of four macaque monkeys. Histological analysis revealed primarily the predicted laminar expression pattern of the optogenetic construct in CamKIIα-rich LGN konio layers, but also showed some expression in parvalbumin positive magno- and parvo cells. We also observed a retrograde tracing mechanism of the AAV5 virus particles that labeled V1 layer 6 cortico-thalamic feedback neurons and retinal ganglion cells. That expression of the construct also allowed modulation of spiking activity in LGN was confirmed in prior electrophysiology experiments. Neurons expressing ChR2 could be identified reliably based on their short latency (