Assembly of functionally antagonistic visual circuits for controlling pupil dynamics

Abstract

HighlightsO_LITbx20 plays a role in the development of non-image-forming pathways.\nC_LIO_LILoss of Tbx20-expressing RGCs alters specific aspects of the pupil reflex arc.\nC_LIO_LIPreviously unknown role for a specific subset of Tbx20-expressing RGCs in modulating pupil size.\nC_LI\n\neTOCDhande et al. identify a novel genetic program that marks and is required for the development of non-image-forming parallel visual pathways. Moreover, chemogenetic activation of a specific retina-to-OPN pathway reveals a novel circuit element controlling pupil size. These findings provide new insight into the mechanisms that establish defining features of functionally specialized sensory pathways.\n\nSummaryThe functional attributes of parallel sensory circuits are determined by the properties of the individual cell types that comprise them, and their connectivity. The mechanisms controlling the specification and establishment of parallel sensory pathways remain unclear. Here we report the non-uniform distribution of retinal ganglion cells (RGCs) expressing the transcription factor Tbx20 in mice. Owing to their layout within the retina, Tbx20-RGCs are positioned to preferentially encode light information from dorsal visual space. We discovered that Tbx20 expression is mostly restricted to three RGC-types: M1 intrinsically photosensitive RGCs (ipRGCs), M2 ipRGCs and diving RGCs. The axonal projections of Tbx20-RGCs innervate non-image-forming brain centers including the suprachiasmatic nucleus, the medial division of the posterior pretectal nucleus, and the olivary pretectal nucleus (OPN), a principal station in the neural pathway for generating the pupillary light reflex (PLR). Conditional deletion of Tbx20 resulted in reduced Tbx20-RGC axonal innervation of these targets and revealed a key role of these neurons in driving specific phases of the PLR. Furthermore, chemogenetic activation uncovered a novel role for a specific subset of Tbx20-RGCs in controlling pupil dilation. These data offer a new understanding of the genetic and molecular mechanisms that establish specific, behaviorally-relevant visual circuits.