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Abstract:
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 (<5ms) spiking responses to direct blue light (473nm) stimulation. Parallel laminar-resolved recordings of the V1 local field potential showed that selective activation of LGN konio layers with optogenetics caused selective electrical current inflow in the supra-granular layers of V1 in agreement with anatomical predictions about the koniocellular projection. Electrical stimulation of LGN konio layers revealed the same supra-granular V1 activation pattern. In contrast, electrical stimulation of LGN parvo layers activated also V1 granular layers in a way that closely resembled visual stimulus driven responses. These findings indicate comparable capacities of both stimulation methods to isolate and identify spatially segregated thalamo-cortical circuit mechanisms of the primate brain.
