Projections of ipRGCs and conventional RGCs to retinorecipient brain nuclei

Abstract

Retinal ganglion cells (RGCs), the output neurons of the retina, allow us to perceive our visual environment. RGCs respond to rod/cone input through the retinal circuitry, however, a small population of RGCs are in addition intrinsically photosensitive (ipRGCs) and project to unique targets in the brain to modulate a broad range of subconscious visual behaviors such as pupil constriction and circadian photoentrainment. Despite the discovery of ipRGCs nearly two decades ago, there is still little information about how or if conventional RGCs (non-ipRGCs) target ipRGC-recipient nuclei to influence subconscious visual behavior. Using a dual recombinase fluorescent reporter strategy, we showed that conventional RGCs innervate many subconscious ipRGC-recipient nuclei, apart from the suprachiasmatic nucleus. We revealed previously unrecognized stratification patterns of retinal innervation from ipRGCs and conventional RGCs in the ventral portion of the lateral geniculate nucleus. Further, we found that the percent innervation of ipRGCs and conventional RGCs across ipsiand contralateral nuclei differ. Our data provide a blueprint to understand how conventional RGCs and ipRGCs innervate different brain regions to influence subconscious visual behaviors.

Divergent outputs of the ventral lateral geniculate nucleus mediate visually evoked defensive behaviors

“…Traditionally, the vLGN was thought to be involved in circadian-related phenomena by virtue of the fact that it receives input from intrinsically photosensitive ''melanopsin'' RGCs (M1 ipRGCs; Harrington, 1997;Berson et al, 2002;Hattar et al, 2006;Chen et al, 2011). However, we and others have observed that the vLGN receives diverse types of retinal inputs in addition to input from M1 ipRGCs (Figure S8;Osterhout et al, 2011;Dhande et al, 2015;Sonoda et al, 2020;Beier et al, 2021). Recent work points to a role for the vLGN in light-mediated effects on depression and spatial memory-processes that occur on the timescale of days (Huang et al, 2019(Huang et al, , 2021.…”

Intrinsic circadian timekeeping properties of the thalamic lateral geniculate nucleus

“…However, optogenetic stimulation of Chronos-expressing slices at the beginning of the projected night was potent to selectively delay activity peak (by ~3 -4.5 h) of the two compartments of VLG, without entraining the IGL. As the VLGm is generally not retinorecipient, or very sparsely innervated by the retina compared to the VLGl (Harrington, 1997;Beier et al, 2020), the phase shift in the VLGm is most likely to be transmitted via the VLGl. This is not surprising, as these two parts of VLG were demonstrated to stay in a strong reciprocal connection (Harrington, 1997;Govindaiah & Cox, 2009;Monavarfeshani et al, 2017).…”

“…Circadian rhythms on the molecular level are reflected in the daytime rise in the electrical activity of the SCN neurons followed by their nocturnal silencing (Belle et al, 2009;Colwell, 2011). Additionally, the SCN is best known for its photoentrainability, as it receives a dense innervation from the retinal ganglion cells (heavily from these synthesising a 'circadian photopigment' melanopsin) and responds to ambient light by both neurophysiological excitation and phase shifts in clock gene expression (Beier et al, 2020).…”

“…The lateral geniculate nucleus (LGN) of the thalamus poses one of the main gateways for photic information conveyed from the retina to the rest of the brain. Specifically, the LGN forms a complex of three independent retinorecipient structures: (1) the dorsolateral geniculate nucleus (DLG), with its thalamo-cortical neurons reaching the primary visual cortex and thus being directly involved in image-forming vision (Sherman, 2005), (2) the intergeniculate leaflet (IGL) implicated in circadian photoentrainment (Albrecht, 2012) (with one of the densest innervation by melanopsin cells; Brown et al, 2010;Beier et al, 2020), but also non-photic behaviours such as modulation of mood, sleep, spatial memory and food intake (Huang et al, 2019(Huang et al, , 2021Shi et al, 2019;Fernandez et al, 2020), and (3) the ventrolateral geniculate nucleus (VLG) associated with visuomotor and other non-image forming functions (Jeannerod & Putkonen, 1971;Legg & Cowey, 1977;Harrington, 1997). The VLG can be further divided into a brainstem input processing medial part (VLGm), and a directly retinorecipient lateral division (VLGl) (Niimi et al, 1963;Takatsuji & Tohyama, 1989;Kolmac & Mitrofanis, 2000).…”

Melanopic Limits of Metamer Spectral Optimisation in Multi-Channel Smart Lighting Systems

“…In the outer retina, six subtypes of ipRGCs (M1 to M6) can be distinguished, each with unique morphological, functional and physiological properties projecting to different targets in the brain [24][25][26][27][28][29][30][31]. The M1-subtype of the ipRGCs directly innervates specific regions of the suprachiasmatic nucleus (SCN) and olivary pretectal nucleus (OPN) to modulate the non-image-forming mechanism involving the circadian photoentrainment and temporal pupil light constriction [15,18,[32][33][34][35][36][37]. In the inner retina, M1-ipRGC dendrites stratify in the outermost sublamina of the inner plexiform layer (IPL), receiving extrinsic synaptic input from rods, L + M-on and inhibitory S-cone signals [26,28,[38][39][40][41][42][43][44][45][46].…”