Impact of age and retinal degeneration on the light input to circadian brain structures

Daniela Lupi,Ma'Ayan Semo,Russell G Foster

doi:10.1016/j.neurobiolaging.2010.03.006

Daniela Lupi, Ma'Ayan Semo + Show 1 more

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https://doi.org/10.1016/j.neurobiolaging.2010.03.006

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Abstract

Aging causes anatomical and functional changes in visual and circadian systems. In wild type mice rods, cones, and photosensitive retinal ganglion cells (pRGCs) decline with age. In rd/rd cl mice, the early loss of rods and cones is followed by protracted transneuronal loss of inner retinal neurons as well as the pRGCs. Here we use Fos induction to study the light input pathway to the suprachiasmatic nuclei (SCN), the intergeniculate leaflets (IGL) and ventral lateral geniculate nuclei (vLGN) of old (∼700 days) and young (∼150 days) wild type and rd/rd cl mice. Cholera toxin tracing was used in parallel to study the anatomy of this pathway. We find that aging rather than retinal degeneration is a more important factor in reducing light input to the SCN, causing both a reduction in Fos expression and retinal afferents. Furthermore, we show light-induced Fos within the vLGN and IGL is predominantly subserved by rods and cones, and once again aging reduces the amplitude of this response.

Highlights

Photoreception in rodents is mediated by rods, cones, and melanopsin-based photosensitive retinal ganglion cells (Hattar et al, 2003; Lucas et al, 2003; Panda et al, 2003; Sekaran et al, 2003)
Analysis of all the integral optical density (IOD) data of Fos immunoreactivity in the suprachiasmatic nuclei (SCN) by three way ANOVA shows: (1) there is a significant effect of light (F1,29 ϭ 108.3, p Ͻ 0.0001), a light pulse causes a substantial increase in Fos immunoreactivity; (2) a significant effect of age (F1,29 ϭ 20.15, p Ͻ 0.0001), older animals show attenuated Fos levels and (3) an interaction between light pulsing and age (F1,29 ϭ 21.58, p Ͻ 0.0001) the amplitude of light induced Fos is reduced in old animals
We show light induction of Fos in both young rd/rd cl and wild type animals and we show that the levels of Fos in the SCN of both genotypes are statistically indistinguishable, indicating that at the cellular level, the have been reported within melanopsin RGCs of aging individuals (Vugler et al, 2007)

Summary

Introduction

Photoreception in rodents is mediated by rods, cones, and melanopsin-based photosensitive retinal ganglion cells (pRGCs) (Hattar et al, 2003; Lucas et al, 2003; Panda et al, 2003; Sekaran et al, 2003). The pRGCs alone are capable of mediating circadian photoentrainment and the phase shifting effect of single pulses of light on activity onset delivered to animals maintained under constant darkness (Barnard et al, 2004; Freedman et al, 1999), and multiple other irradiance detection tasks including the suppression of pineal melatonin (Lucas et al, 1999), pupil constriction (Lucas et al, 2001), negative masking behavior (Thompson et al, 2008) and the modulation of sleep (Altimus et al, 2008; Lupi et al, 2008) Aging affects both the retina and circadian system. While the vLGN shows upregulation of Fos in response to light, any role it may have in circadian organization remains unresolved (Prichard et al, 2002; Rusak et al, 1990)

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