Divergent projection patterns of M1 ipRGC subtypes

Abstract

In addition to its well-known role in pattern vision, light influences a wide range of non-image forming, subconscious visual behaviors including circadian photoentrainment, sleep, mood, learning, and the pupillary light reflex. Each of these behaviors is thought to require input from the M1 subtype of melanopsin-expressing, intrinsically photosensitive retinal ganglion cell (ipRGC). Recent work has demonstrated that the M1 subtype of ipRGC can be further subdivided based on expression of the transcription factor Brn3b. Brn3b-positive M1 ipRGCs project to the olivary pretectal nucleus and are necessary for the pupillary light reflex, while Brn3b-negative M1 ipRGCs project to the suprachiasmatic nucleus (SCN) and are sufficient for circadian photoentrainment. However, beyond the circadian and pupil systems, little is known about the projection patterns of M1 ipRGC subtypes. Here we show that Brn3b-positive M1 ipRGCs comprise the majority of sparse M1 ipRGC inputs to the thalamus, midbrain, and hypothalamus. Our data demonstrate that very few brain targets receive convergent input from both M1 ipRGC subpopulations, suggesting that each subpopulation drives a specific subset of light-driven behaviors.

Distinct ipRGC subpopulations mediate light's acute and circadian effects on body temperature and sleep

“…A majority of all known ipRGC subtypes (M1-M5) are lost in Brn3b-DTA mice (Chen et al, 2011), with the exception of a subset of ~200 M1 ipRGCs. In agreement with this, ipRGC projections to all minor hypothalamic targets are lost in Brn3b-DTA mice, while innervation of the SCN and part of the IGL remains intact (Chen et al 2011, Li and Schmidt, 2018). This suggests that all non-M1 subtypes and a portion of M1 ipRGCs are Brn3b(+).…”

Chromatic Pupillometry Findings in Alzheimer’s Disease

“…In this study we included AD patients in a mild-moderate stage of the disease and disease severity and duration were on average lower than previously published cohorts (La Morgia et al, 2016). In rodents, six different mRGC subtypes were characterized, and PLR was mainly regulated by the Brn3b-positive M1 and non-M1 subtypes (Chen et al, 2011;Li and Schmidt, 2018). In humans, Hannibal and colleagues also identified six subtypes of mRGCs (M1, M2, M3, M4, giant M1, and giant displaced M1), unevenly distributed across the human retina and with distinct anatomical characteristics (Hannibal et al, 2017).…”

“…Melanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive RGCs because of the expression of the photopigment melanopsin ( Berson et al, 2002 ; Hannibal et al, 2002 ; Hattar et al, 2002 ). These cells contribute to non-image forming functions of the eye including circadian photoentrainment [projecting via the retino-hypothalamic tract (RHT) to the suprachiasmatic nucleus (SCN) of the hypothalamus] and regulation of the pupillary light reflex (PLR) [via projections to the olivary pretectal nucleus (OPN)] ( Sadun et al, 1984 ; Hannibal et al, 2004 , 2014 ; Baver et al, 2008 ; Chen et al, 2011 ; Li and Schmidt, 2018 ).…”

M1 Intrinsically Photosensitive Retinal Ganglion Cells Integrate Rod and Melanopsin Inputs to Signal in Low Light

“…The non-image-forming visual system is responsible for mediating a range of light-driven processes, including circadian photoentrainment, the pupillary light reflex, masking, mood modulation, and hormonal regulation. These myriad functions are thought to be primarily mediated by the M1 subtype of melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs), which directly project to more than 15 nonimage-forming brain regions to execute these functions (Fernandez et al, 2016;G€ uler et al, 2008;Hattar et al, 2006;Li and Schmidt, 2018).…”