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T. M. Brown, J. Gigg, H. D. Piggins, R. J. Lucas; Melanopsin-Dependent Activation of Dorsal Lateral Geniculate Neurons. Invest. Ophthalmol. Vis. Sci. 2010;51(13):672.
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A subset of retinal ganglion cells, that express melanopsin, are intrinsically photosensitive (ipRGCs). These cells are known to innervate brain nuclei that mediate non-image-forming visual responses but projections to regions involved in conventional vision have not been observed. Since it is now clear that ipRGC subtypes with unknown projection patterns exist, we investigated the possibility that ipRGCs influence neuronal activity in the dLGN, thalamic relay to the visual cortex.
We recorded neuronal activity from the LGN of urethane anaesthetised mice, using multichannel silicon probes, and assessed responses to light steps (60s) delivered by an LED light source, providing full field, uniform, illumination of the contralateral retina.
Initially, we recorded responses to 460nm light in adult mice lacking rods and cones (rd/rd cl). Light responses in these mice exhibited characteristic features of melanopisn photoreception; slow kinetics, steep irradiance response function and high response threshold. Surprisingly, responsive cells were found throughout the LGN (~35% of all units detected) including many in the dLGN. To determine whether this reflected compensatory changes in rd/rd cl mice, we next recorded from human red cone knockin mice (Opn1mwR), in which any cone dependent response can be identified by its anomalous sensitivity to red light. In these mice we observed a high proportion of cells (~40%) throughout the LGN that, in addition to robust on/off transients, exhibited sustained activations to 60s bright light with a spectral sensitivity consistent with that of melanopsin. As confirmation that these responses derived from melanopsin we employed melanopsin knockout mice (Opn4-/-). LGN neurons in these animals maintained robust transient responses at light on and off but were strikingly unable to sustain elevated firing rates throughout the course of a 60s stimuli.
Melanopsin exerts a pronounced influence on dLGN neurons, with melanopsin signals evident in the activity of almost half of all light responsive cells in this region. These findings represent the first description of melanopsin-dependent activity in centres responsible for conventional visual processing.
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