Seasonal and post-trauma remodeling in cone-dominant ground squirrel retina

Abstract

With a photoreceptor mosaic containing ~85% cones, the ground squirrel is one of the richest known mammalian sources of these important retinal cells. It also has a visual ecology much like the human’s. While the ground squirrel retina is understandably prominent in the cone biochemistry, physiology, and circuitry literature, far less is known about the remodeling potential of its retinal pigment epithelium, neurons, macroglia, or microglia. This review aims to summarize the data from ground squirrel retina to this point in time, and to relate them to data from other brain areas where appropriate. We begin with a survey of the ground squirrel visual system, making comparisons with traditional rodent models and with human. Because this animal’s status as a hibernator often goes unnoticed in the vision literature, we then present a brief primer on hibernation biology. Next we review what is known about ground squirrel retinal remodeling concurrent with deep torpor and with rapid recovery upon re-warming. Notable here is rapidly-reversible, temperature-dependent structural plasticity of cone ribbon synapses, as well as pre- and post-synaptic plasticity throughout diverse brain regions. It is not yet clear if retinal cell types other than cones engage in torpor-associated synaptic remodeling. We end with the small but intriguing literature on the ground squirrel retina’s remodeling responses to insult by retinal detachment. Notable for widespread loss of (cone) photoreceptors, there is surprisingly little remodeling of the RPE or Müller cells. Microglial activation appears minimal, and remodeling of surviving second- and third-order neurons seems absent, but both require further study. In contrast, traumatic brain injury in the ground squirrel elicits typical macroglial and microglial responses. Overall, the data to date strongly suggest a heretofore unrecognized, natural checkpoint between retinal deafferentiation and RPE and Müller cell remodeling events. As we continue to discover them, the unique ways by which ground squirrel retina responds to hibernation or injury may be adaptable to therapeutic use.

Molecular Prerequisites for Diminished Cold Sensitivity in Ground Squirrels and Hamsters

“…In contrast to mice or rats, ground squirrels and hamsters can undergo prolonged periods of hibernation, during which their core body temperature drops to ambient and can be as low as 2°C–7°C (Bouma et al 2011, Merriman et al 2016, Carey et al 2003, Tupone et al 2017). While the mechanism of hibernation is complex and poorly understood, it seems clear that it involves significant modifications to the animal’s thermoregulatory responses, which normally rely on the integration and processing of inputs from both peripheral and internal thermosensory systems (Almeida et al 2012, Weidler et al 1974, Heller and Colliver 1974).…”

Evolutionary loss of cone photoreception in balaenid whales reveals circuit stability in the mammalian retina

“…Cone cell signaling is maintained in other mammals experiencing important changes in their photoreceptors. In hibernating ground squirrels, for example, a variety of retinal changes take place including “deconstruction” of cone outer segments, mitochondria in cone elipsoids, and cone ribbon synapses (for review, see Merriman et al, ), but these changes have little effect on cone synaptic communication (Mehta et al, ). In the experimentally detached retina of the domestic cat, whereas rods undergo reconfiguration of their synapses and withdrawal of their axons, apparently normal cone synapses can be maintained (Fisher et al, ).…”

Assessment of Outer Retinal Remodeling in the Hibernating 13-Lined Ground Squirrel

“…Limited work has suggested reversibly shortened (or potentially eliminated) photoreceptor OS, depleted IS mitochondria, and remodeled ribbon synapses. 16 – 19 Such retinal changes provide an “experiment of nature” to probe the subcellular origin of the outer reflective signals seen with OCT retinal imaging. We leveraged the natural and reversible structural phenotypes of the torpid 13-LGS photoreceptors to better understand how this outer retinal remodeling affects OCT outer hyperreflective bands, and how these patterns compare with histologic structure.…”