The 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 1 0 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 color 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 ipsi-and contralateral nuclei differ. Our data provide a blueprint to understand how conventional RGCs and ipRGCs innervate different 2 0 brain regions to influence subconscious visual behaviors. 3 0 forming visual behaviors (Altimus et al., information about how or if conventional RGCs (non-ipRGCs) can influence subconscious visual behaviors. To address this knowledge gap, we must first delineate whether conventional RGCs innervate non-image forming nuclei.To determine if conventional RGCs innervate non-image forming nuclei (Ecker et al., 2010; Hattar et al., 2002 Hattar et al., , 2006 Li and Schmidt, 2018; Morin and Studholme, 2014), we utilized a dual recombinase two color strategy to delineate, in the same animal, how ipRGCs and conventional RGCs converge and diverge in ipRGC-recipient brain regions. We found that the master clock in the suprachiasmatic nucleus (SCN) is exclusively innervated by ipRGCs, as was previously 4 0 implicated (Hattar et al., 2006). However, the SCN was the exception to the rule, as most ipRGC-recipient areas received substantial projections from conventional RGCs. The dual color strategy allowed us to differentiate areas where conventional RGCs and ipRGCs converge and intermingle, from brain regions where they form completely distinct subdivisions. Specifically, we found that conventional RGCs and ipRGCs innervate distinct subdivisions of the ventral lateral geniculate nucleus (vLGN). As we found in the SCN, the vLGN core region receives exclusive ipRGC input. Furthermore, we found differences in the percent innervation between the ipsi-and contralateral patterns of conventional RGCs and ipRGCs. Our results provide a basis for understanding how ipRGCs and conventional RGC modulate non-image forming behaviors for normal function. 5 0

Ultrastructure of synaptic connectivity within sub-regions of the SCN revealed by genetically encoded EM tag and SBEM

“…Together, these data showed an equally dense mRGC projection into both regions of the SCN and a stronger synaptic connection between mRGC and the shell SCN which should still be evaluated further. Agreeing with our observation, early studies also show direct retinal innervation of both the ventral and dorsal SCN (Beier et al, 2020; Hattar et al, 2006). On the contrary, it was reported that the ventral SCN was reported to receive most of the retinal input and transfer this input to the dorsal SCN (Abrahamson & Moore, 2001; Kriegsfeld et al, 2004; Moore et al, 2002; Welsh et al, 2010).…”

Divergent outer retinal circuits drive image and non-image visual behaviors

“…However, this conclusion ignores the fact that it is unknown whether other non-M1 ipRGCs and non-ipRGCs drive or modulate non-image-forming behaviors. Brain regions that play a central role in non-image-forming vision receive diverse ipRGC and non-ipRGC innervation ( Baver et al, 2008 ; Beier et al, 2020 ; Quattrochi et al, 2019 ). The makeup of RGC innervation to non-image-forming brain regions will ultimately influence behavior; for example, genetically ablating the M1 ipRGC abolishes an animal’s ability to photoentrain, but some PLR remains ( Güler et al, 2008 ).…”

Endogenous opioid signaling in the retina modulates sleep/wake activity in mice

“…Indeed, a series of studies proved that melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are the sole conduit of photoentrainment ( Berson, 2003 ; Güler et al, 2008 ). In addition to transmitting light information to the suprachiasmatic nucleus (SCN) ( Fernandez et al, 2016 ), ipRGCs send monosynaptic projections to sleep-promoting centers, such as the preoptic area ( Hattar et al, 2006 ; Beier et al, 2021 ), to mediate the acute effects of light on sleep ( Altimus et al, 2008 ; Lupi et al, 2008 ; Zhang et al, 2021 ). Neuromodulatory processes inhibiting ipRGCs are expected to alter light-evoked behaviors mediated by ipRGCs, such as photoentrainment and/or pupillary light reflex (PLR) ( Güler et al, 2008 ).…”