Optogenetic suppression of corticogeniculate feedback in anesthetized ferrets is overridden by visual stimulation

The feedforward projection from the retina shapes the spatial receptive field properties of neurons in the dorsal lateral geniculate nucleus of the thalamus (LGN). Corticogeniculate feedback from the visual cortex appears to exert a more subtle, modulatory influence on LGN responses. Studies involving manipulations of corticogeniculate feedback have yielded inconsistent findings, but the reasons for these inconsistencies are not known. To examine the functional contributions of corticogeniculate feedback, and to resolve past inconsistencies, we examined the effects of selective optogenetic suppression of corticogeniculate neurons in anesthetized ferrets. In particular, we examined the responses of LGN and V1 neurons during optogenetic suppression of corticogeniculate feedback in the presence and absence of visual stimulation and across conditions in which the frequency of LED illumination varied. Optogenetic suppression of corticogeniculate feedback decreased activity among LGN neurons in the absence of visual stimulation, dispelling the notion that anesthesia causes a floor effect. In contrast, suppressing corticogeniculate feedback did not affect the visual responses of LGN neurons, suggesting that feedforward visual stimulus drive overrides weak corticogeniculate influence. Optogenetic effects on LGN and V1 neuronal responses depended on the frequency of LED illumination, with higher frequency illumination inducing slow oscillations in V1, dis-inhibiting V1 neurons locally, and producing more suppression among LGN neurons. These results demonstrate that corticogeniculate influence depends on stimulation parameters including visual stimulus conditions and frequency of inactivation. Furthermore, weak corticogeniculate influence is overridden by strong feedforward visual stimulus drive - this attribute is the most likely source of inconsistencies in past studies. Significance StatementAlthough corticogeniculate synapses onto thalamic neurons far outnumber those coming from the retina, the function of corticogeniculate feedback in vision has remained a stubborn puzzle. Prior studies of corticogeniculate feedback have yielded inconsistent findings, but the source for these inconsistencies is unknown. We utilized selective optogenetic suppression of corticogeniculate feedback to examine its effects on thalamic neuronal responses and to resolve sources of prior inconsistencies. We found that suppression of corticogeniculate feedback reduced thalamic responses, but only in the absence of visual input. This suggests that the major source of inconsistencies across prior studies is the fact that weak corticogeniculate influence is overcome by strong feedforward visual stimulus drive.