Abstract
Proper circadian photoentrainment is crucial for the survival of many organisms. In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) can use the photopigment melanopsin to sense light independently from rod and cone photoreceptors and send this information to many brain nuclei such as the suprachiasmatic nucleus (SCN), the site of the central circadian pacemaker. Here, we measure ionic currents and develop mathematical models of the electrical activity of two types of ipRGCs: M1, which projects to the SCN, and M4, which does not. We illustrate how their ionic properties differ, mainly how ionic currents generate lower spike rates and depolarization block in M1 ipRGCs. Both M1 and M4 cells have large geometries and project to higher visual centers of the brain via the optic nerve. Using a partial differential equation model, we show how axons of M1 and M4 cells faithfully convey information from the soma to the synapse even when the signal at the soma is attenuated due to depolarization block. Finally, we consider an ionic model of circadian photoentrainment from ipRGCs synapsing on SCN neurons and show how the properties of M1 ipRGCs are tuned to create accurate transmission of visual signals from the retina to the central pacemaker, whereas M4 ipRGCs would not evoke nearly as efficient a postsynaptic response. This work shows how ipRGCs and SCN neurons' electrical activities are tuned to allow for accurate circadian photoentrainment.
Highlights
Unlike rod and cone photoreceptors, which signal to the brain via second-and third-order retinal neurons, intrinsically photosensitive retinal ganglion cells communicate light information directly to the brain (Berson et al, 2002; Dacey et al, 2005; Hattar et al, 2006)
Intracellular dye fills enabled the identification of the recorded intrinsically photosensitive retinal ganglion cells (ipRGCs) based on morphological criteria: M1 cells had mediumsized somas and sparse dendrites stratifying in the OFF sublamina, whereas M4 cells had giant somas and dense, radiate dendrites stratifying near the retinal surface (Ecker et al, 2010; Estevez et al, 2012)
We developed mathematical models of M1 and M4 ipRGC electrophysiology using the Hodgkin-Huxley formalism
Summary
Unlike rod and cone photoreceptors, which signal to the brain via second-and third-order retinal neurons, intrinsically photosensitive retinal ganglion cells (ipRGCs) communicate light information directly to the brain (Berson et al, 2002; Dacey et al, 2005; Hattar et al, 2006). Since their discovery in the early 2000s, ipRGCs have been investigated extensively, with multiple. Modeling ipRGCs and Photoentrainment types and functional roles identified for the cells (Baver et al, 2008; Ecker et al, 2010; Li and Schmidt, 2018). M4 cells have received attention for their role in imageforming vision and contrast sensitivity (Estevez et al, 2012; Schmidt et al, 2014; Zhao et al, 2014; Schroeder et al, 2018)
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