skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on March 7, 2027

Title: Respiratory Modulation by Phototransduction Demonstrates Time-Dependence in Male Mice
The transduction of light energy at the retina goes on to affect a range of non-image forming processes, most notably circadian photoentrainment, mood, and the pupillary light reflex. Our lab has previously demonstrated that retinal phototransduction can also modulate an animal’s breathing. However, it remains unknown how the timing of a light stimulus alters phototransduction and resulting behavior. Here, we investigate how unpredictable light stimuli affect respiratory frequency and tidal volume in mice. Male C57BL/6J mice (n = 8) were maintained on a 12:12 light–dark cycle, and breathing was assessed using whole-body plethysmography. All light stimuli were presented during the animals’ dark phase, either 1 hour after lights off (“early” dark phase, ZT13 to ZT16) or 5 hours after lights off (“late” dark phase, ZT17 to ZT20). As supported by our prior research, early light stimuli immediately suppressed breathing and, later, led to an increase in breathing after stimuli offset. However, late dark phase stimuli failed to affect respiration, even when spectral composition of the light was modified. These data demonstrate that the timing of light has differential effects on breathing. These data may implicate time-dependent differences in phototransduction and/or time-dependent differences in signal processing which go on to affect fundamental physiological processes.  more » « less
Award ID(s):
2440777
PAR ID:
10650444
Author(s) / Creator(s):
; ;
Publisher / Repository:
ASBMB Annual Meeting
Date Published:
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Respiratory frequency and tidal volume exhibit daily, 24-hr rhythms in human and rodent models. Environmental light has emerged as a potential modulator of ventilatory rhythmicity, as mice lacking intrinsically photosensitive retinal ganglion cells fail to alter their breathing in response to light. Despite this evidence, it remains unknown how the duration of light exposure influences breathing in mice. To assess the effects of light exposure on breathing, male wild-type mice (n = 8) were exposed to broad-spectrum white light (~450 lux) in the standard dark phase, either for 3h (ZT 13-16) or for 5 minutes (ZT13-13.05). Respiratory measures were assessed for 36 hours using whole-body plethysmography. To determine whether the light manipulation produced significant deviations from expected respiratory patterns, a nonparametric, within-subjects bootstrapping approach was conducted in R. This compared parallel time points between a predefined test period and the equivalent control period without a light manipulation. We found that a 3h light stimulus administered during the standard dark phase reduced tidal volume and respiratory frequency for ~80 minutes during light exposure. Immediately following the offset of the 3h stimulus, respiratory frequency was increased for 2h compared to control. While statistical analysis is currently ongoing, a 5-minute light stimulus appeared to decrease both tidal volume and respiratory frequency during light exposure. In contrast to a 3hr stimulus, both tidal volume and respiratory frequency were increased at 90 minutes following the offset of the 5-minute light stimulus. While preliminary, these data suggest that tidal volume and respiratory frequency differentially respond to the duration of environmental light exposure. Subsequent research is required to determine if tidal volume is specifically responsive to shorter light durations and the extent to which a 3h light stimulus may be “masking” the tidal volume response. This work expands upon our current understanding of respiratory physiology to include light duration as a key variable affecting daily breathing 
    more » « less
  2. Shift work chronically disrupts circadian rhythms and increases the risk of developing cardiovascular disease. However, the mechanisms linking shift work and cardiovascular disease are largely unknown. The goal of this study was to investigate the effects of chronically shifting the light-dark (LD) cycle, which models the disordered exposure to light that may occur during shift work, on atherosclerosis. Atherosclerosis is the progressive accumulation of lipid-filled lesions within the artery wall and is the leading cause of cardiovascular disease. We studied ApolipoproteinE -deficient ( ApoE −/− ) mice that are a well-established model of atherosclerosis. Male and female ApoE −/− mice were housed in control 12L:12D or chronic LD shift conditions for 12 weeks and fed low-fat diet. In the chronic LD shift condition, the light-dark cycle was advanced by 6 h every week. We found that chronic LD shifts exacerbated atherosclerosis in female, but not male, ApoE −/− mice. In females, chronic LD shifts increased total serum cholesterol concentrations with increased atherogenic VLDL/LDL particles. Chronic LD shifts did not affect food intake, activity, or body weight in male or female ApoE −/− mice. We also examined eating behavior in female ApoE −/− mice since aberrant meal timing has been linked to atherosclerosis. The phases of eating behavior rhythms, like locomotor activity rhythms, gradually shifted to the new LD cycle each week in the chronic LD shift group, but there was no effect of the LD shift on the amplitudes of the eating rhythms. Moreover, the duration of fasting intervals was not different in control 12L:12D compared to chronic LD shift conditions. Together these data demonstrate that female ApoE −/− mice have increased atherosclerosis when exposed to chronic LD shifts due to increased VLDL/LDL cholesterol, independent of changes in energy balance or feeding-fasting cycles. 
    more » « less
  3. Cerebellar granule cells (GrCs) are usually regarded as a uniform cell type that collectively expands the coding space of the cerebellum by integrating diverse combinations of mossy fiber inputs. Accordingly, stable molecularly or physiologically defined GrC subtypes within a single cerebellar region have not been reported. The only known cellular property that distinguishes otherwise homogeneous GrCs is the correspondence between GrC birth timing and the depth of the molecular layer to which their axons project. To determine the role birth timing plays in GrC wiring and function, we developed genetic strategies to access early- and late-born GrCs. We initiated retrograde monosynaptic rabies virus tracing from control (birth timing unrestricted), early-born, and late-born GrCs, revealing the different patterns of mossy fiber input to GrCs in vermis lobule 6 and simplex, as well as to early- and late-born GrCs of vermis lobule 6: sensory and motor nuclei provide more input to early-born GrCs, while basal pontine and cerebellar nuclei provide more input to late-born GrCs. In vivo multidepth two-photon Ca 2+ imaging of axons of early- and late-born GrCs revealed representations of diverse task variables and stimuli by both populations, with modest differences in the proportions encoding movement, reward anticipation, and reward consumption. Our results suggest neither organized parallel processing nor completely random organization of mossy fiber→GrC circuitry but instead a moderate influence of birth timing on GrC wiring and encoding. Our imaging data also provide evidence that GrCs can represent generalized responses to aversive stimuli, in addition to recently described reward representations. 
    more » « less
  4. Abstract Vision is underpinned by phototransduction, a signaling cascade that converts light energy into an electrical signal. Among insects, phototransduction is best understood in Drosophila melanogaster. Comparison of D. melanogaster against three insect species found several phototransduction gene gains and losses, however, lepidopterans were not examined. Diurnal butterflies and nocturnal moths occupy different light environments and have distinct eye morphologies, which might impact the expression of their phototransduction genes. Here we investigated: 1) how phototransduction genes vary in gene gain or loss between D. melanogaster and Lepidoptera, and 2) variations in phototransduction genes between moths and butterflies. To test our prediction of phototransduction differences due to distinct visual ecologies, we used insect reference genomes, phylogenetics, and moth and butterfly head RNA-Seq and transcriptome data. As expected, most phototransduction genes were conserved between D. melanogaster and Lepidoptera, with some exceptions. Notably, we found two lepidopteran opsins lacking a D. melanogaster ortholog. Using antibodies we found that one of these opsins, a candidate retinochrome, which we refer to as unclassified opsin (UnRh), is expressed in the crystalline cone cells and the pigment cells of the butterfly, Heliconius melpomene. Our results also show that butterflies express similar amounts of trp and trpl channel mRNAs, whereas moths express ∼50× less trp, a potential adaptation to darkness. Our findings suggest that while many single-copy D. melanogaster phototransduction genes are conserved in lepidopterans, phototransduction gene expression differences exist between moths and butterflies that may be linked to their visual light environment. 
    more » « less
  5. The inhibition of hypocotyl elongation by ethylene in dark-grown seedlings was the basis of elegant screens that identified ethylene-insensitive Arabidopsis mutants, which remained tall even when treated with high concentrations of ethylene. This simple approach proved invaluable for identification and molecular characterization of major players in the ethylene signaling and response pathway, including receptors and downstream signaling proteins, as well as transcription factors that mediate the extensive transcriptional remodeling observed in response to elevated ethylene. However, the dark-adapted early developmental stage used in these experiments represents only a small segment of a plant’s life cycle. After a seedling’s emergence from the soil, light signaling pathways elicit a switch in developmental programming and the hormonal circuitry that controls it. Accordingly, ethylene levels and responses diverge under these different environmental conditions. In this review, we compare and contrast ethylene synthesis, perception, and response in light and dark contexts, including the molecular mechanisms linking light responses to ethylene biology. One powerful method to identify similarities and differences in these important regulatory processes is through comparison of transcriptomic datasets resulting from manipulation of ethylene levels or signaling under varying light conditions. We performed a meta-analysis of multiple transcriptomic datasets to uncover transcriptional responses to ethylene that are both light-dependent and light-independent. We identified a core set of 139 transcripts with robust and consistent responses to elevated ethylene across three root-specific datasets. This “gold standard” group of ethylene-regulated transcripts includes mRNAs encoding numerous proteins that function in ethylene signaling and synthesis, but also reveals a number of previously uncharacterized gene products that may contribute to ethylene response phenotypes. Understanding these light-dependent differences in ethylene signaling and synthesis will provide greater insight into the roles of ethylene in growth and development across the entire plant life cycle. 
    more » « less