Proceedings of The Physiological Society

Cardiff University (2009) Proc Physiol Soc 17, C08

Oral Communications

Widespread activation of the thalamo-cortical visual pathway by melanopsin photoreceptors.

T. M. Brown1, C. Gias2, M. Semo2, P. J. Coffey2, J. Gigg1, H. D. Piggins1, R. J. Lucas1

1. Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom. 2. Institute of Ophthalmology, University College London, London, United Kingdom.

A subset of retinal ganglion cells, that express melanopsin, are intrinsically photosensitive (ipRGCs). Activity of these ipRGCs defines responses to environmental irradiance such as circadian photoentrainment and the pupil light reflex, but a role in image-forming vision has been widely discounted since projections to the dorsal lateral geniculate (dLGN; thalamic relay to the visual cortex) have not been observed. Since it has now clear that the marker used to track ipRGC projections in earlier studies only labels ~50% of ipRGCs, we revisited the possibility that ipRGCs contribute to image-forming visual processing. We investigated how melanopsin signals influenced neural activity in the visual thalamus using multichannel extracellular recordings in urethane anaesthetised mice (1.7g/kg). In mice lacking rods and cones (rd/rd cl), full field illumination of the contralateral eye (460±10nm) evoked excitatory responses in a large proportion (~40%, n=1051) of cells throughout the ventral and dorsal LGN. To determine whether this widespread appearance of melanopsin signals in the LGN reflected compensatory changes in rd/rd cl mice, we turned to red cone knockin mice (Opn1mwR). These animals have a fully intact retina, but cone-dependent responses can be identified by their anomalous sensitivity to red light. In these mice, all light-responsive cells (n=248) showed rod/cone mediated transient changes in spike rate at light on/off. However, almost half of these cells also exhibited sustained responses to 60s bright light that could not have been mediated via rods or cones. To confirm that these sustained responses originated with melanopsin we used melanopsin knockout mice. LGN neurons in these animals maintained robust transient responses at light on/off (n=217), however, unlike cells in rd/rd cl and Opn1mwR mice, were unable to sustain elevated firing rates throughout a 60s stimuli. Finally we used intrinsic optical imaging to determine whether these melanopsin signals evident in the dLGN were conveyed to higher visual centres. We found a robust light-activation of V1, V2M and retrosplenial cortex in rd/rd cl mice that was almost identical to that of wildtype (both n=6) at all but the shortest timescales. In conclusion, our data indicate that the thalamo-cortical visual pathway is a principal target of melanopsin photoreception.

Where applicable, experiments conform with Society ethical requirements