Patterns of diel activity-how animals allocate their activity throughout the 24-h daily cycle-play key roles in shaping the internal physiology of an animal and its relationship with the external ...environment.
Although shifts in diel activity patterns have occurred numerous times over the course of vertebrate evolution,
the genomic correlates of such transitions remain unknown. Here, we use the African striped mouse (Rhabdomys pumilio), a species that transitioned from the ancestrally nocturnal diel niche of its close relatives to a diurnal one,
to define patterns of naturally occurring molecular variation in diel niche traits. First, to facilitate genomic analyses, we generate a chromosome-level genome assembly of the striped mouse. Next, using transcriptomics, we show that the switch to daytime activity in this species is associated with a realignment of daily rhythms in peripheral tissues with respect to the light:dark cycle and the central circadian clock. To uncover selection pressures associated with this temporal niche shift, we perform comparative genomic analyses with closely related rodent species and find evidence of relaxation of purifying selection on striped mouse genes in the rod phototransduction pathway. In agreement with this, electroretinogram measurements demonstrate that striped mice have functional differences in dim-light visual responses compared with nocturnal rodents. Taken together, our results show that striped mice have undergone a drastic change in circadian organization and provide evidence that the visual system has been a major target of selection as this species transitioned to a novel temporal niche.
The collective activity pattern of retinal ganglion cells, the retinal code, underlies higher visual processing. How does the ambient illuminance of the visual scene influence this retinal output? We ...recorded from isolated mouse and pig retina and from mouse dorsal lateral geniculate nucleus in vivo at up to seven ambient light levels covering the scotopic to photopic regimes. Across each luminance transition, most ganglion cells exhibited qualitative response changes, whereas they maintained stable responses within each luminance. We commonly observed the appearance and disappearance of ON responses in OFF cells and vice versa. Such qualitative response changes occurred for a variety of stimuli, including full-field and localized contrast steps and naturalistic movies. Our results suggest that the retinal code is not fixed but varies with every change of ambient luminance. This finding raises questions about signal processing within the retina and has implications for visual processing in higher brain areas.
To describe the activity of rods and cones in visually intact mice in mesopic conditions, and establish the relative importance of each photoreceptor type in defining the transition from rod to cone ...vision.
Using mice (Opn1mwR) carrying a red-shifted cone opsin, we applied silent substitution methods to record light-adapted ERGs to flash stimuli visible only to rods or cones across a range of light levels (corneal irradiance 10⁹-10¹⁴ photons/cm²/s; ∼10⁰-10⁶ photoisomerisations/rod/s). We tested the impact of selectively changing the background light intensity as experienced by cones on the rod ERG (and vice versa) by adjusting the spectral composition of stimuli. The ERG parameters (b-wave amplitude and implicit time, oscillatory power) were extracted, and their relationship to background intensity and the effective irradiance for cones versus rods/melanopsin was established. We also attempted to record a melanopsin ERG by using modifications of the rod-isolating stimuli.
We saw the predicted decay and increase in rod- and cone-ERG amplitude, respectively, as a function of background intensity. There was only a single irradiance (10¹³ photons/cm²/s) at which both ERGs had high amplitude. Adjustments in the effective irradiance for rods/melanopsin did not impact the cone ERG except at the brightest backgrounds at which there was a melanopsin-dependent suppression of b-wave amplitude. Increasing effective irradiance for cones suppressed rod b-wave amplitude across all background intensities. In addition, we were unable to record a melanopsin ERG.
The cone measure of irradiance was particularly important in driving the transition from rod- to cone-based vision across mesopic light levels.
Melanopsin photoreception plays a vital role in irradiance detection for non-image forming responses to light. However, little is known about the involvement of melanopsin in emotional processing of ...luminance. When confronted with a gradient in light, organisms exhibit spatial movements relative to this stimulus. In rodents, behavioural light aversion (BLA) is a well-documented but poorly understood phenomenon during which animals attribute salience to light and remove themselves from it. Here, using genetically modified mice and an open field behavioural paradigm, we investigate the role of melanopsin in BLA. While wildtype (WT), melanopsin knockout (Opn4(-/-)) and rd/rd cl (melanopsin only (MO)) mice all exhibit BLA, our novel methodology reveals that isolated melanopsin photoreception produces a slow, potentiating response to light. In order to control for the involvement of pupillary constriction in BLA we eliminated this variable with topical atropine application. This manipulation enhanced BLA in WT and MO mice, but most remarkably, revealed light aversion in triple knockout (TKO) mice, lacking three elements deemed essential for conventional photoreception (Opn4(-/-) Gnat1(-/-) Cnga3(-/-)). Using a number of complementary strategies, we determined this response to be generated at the level of the retina. Our findings have significant implications for the understanding of how melanopsin signalling may modulate aversive responses to light in mice and humans. In addition, we also reveal a clear potential for light perception in TKO mice.
Can We See with Melanopsin? Lucas, Robert J; Allen, Annette E; Milosavljevic, Nina ...
Annual review of vision science,
09/2020, Letnik:
6, Številka:
1
Journal Article
Recenzirano
Odprti dostop
A small fraction of mammalian retinal ganglion cells are directly photoreceptive thanks to their expression of the photopigment melanopsin. These intrinsically photosensitive retinal ganglion cells ...(ipRGCs) have well-established roles in a variety of reflex responses to changes in ambient light intensity, including circadian photoentrainment. In this article, we review the growing evidence, obtained primarily from laboratory mice and humans, that the ability to sense light via melanopsin is also an important component of perceptual and form vision. Melanopsin photoreception has low temporal resolution, making it fundamentally biased toward detecting changes in ambient light and coarse patterns rather than fine details. Nevertheless, melanopsin can indirectly impact high-acuity vision by driving aspects of light adaptation ranging from pupil constriction to changes in visual circuit performance. Melanopsin also contributes directly to perceptions of brightness, and recent data suggest that this influences the appearance not only of overall scene brightness, but also of low-frequency patterns.
Background and Purpose
Inhibition of monocarboxylate transport 1 (MCT1) is of interest in targeting highly glycolytic tumours. However, MCT1 is expressed in retina, and so inhibition of MCT1 could ...affect retinal function.
Experimental Approach
AZD3965, an MCT1 inhibitor selected for clinical development, and two additional MCT1 inhibitors were evaluated for effects on visual acuity in albino (Han Wistar) rats. The effects of AZD3965 on visual acuity and electroretinography (ERG) were further investigated in pigmented (Long‐Evans) rats, with dosing for up to 7 days.
Key Results
All three MCT1 inhibitors reduced visual acuity within 2 h of dosing, suggesting a class effect. The deficit caused by AZD3965 (1,000 mg·kg−1 p.o. per day for 4 days) in Long Evans rats recovered to pre‐dose levels 7 days after cessation of dosing. AZD3965 (50 to 1,000 mg·kg−1 p.o.) reduced the amplitude of scotopic a‐ and b‐waves, and photopic b‐wave of the ERG in a dose‐related fashion, within 2 h of dosing. The effects on the scotopic ERG had diminished by Day 7 of dosing, demonstrating partial restoration of function despite continued treatment. Seven days after cessation of dosing at the highest dose tested (1,000 mg·kg−1), there was recovery of both scotopic a‐ and b‐ waves and, to a lesser extent, photopic b‐wave. ERG was affected at lower plasma exposures than was visual function.
Conclusions and Implications
This study clarifies the role of the MCT1 transporter in retinal function. The monitorability of the functional effects on the retina enabled safe clinical use of AZD3965.
Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and project to central targets, allowing them to contribute to both image-forming and non-image ...forming vision. Recent studies have highlighted chemical and electrical synapses between ipRGCs and neurons of the inner retina, suggesting a potential influence from the melanopsin-born signal to affect visual processing at an early stage of the visual pathway. We investigated melanopsin responses in ganglion cell layer (GCL) neurons of both intact and dystrophic mouse retinas using 256 channel multi-electrode array (MEA) recordings. A wide 200 μm inter-electrode spacing enabled a pan-retinal visualization of melanopsin's influence upon GCL activity. Upon initial stimulation of dystrophic retinas with a long, bright light pulse, over 37% of units responded with an increase in firing (a far greater fraction than can be expected from the anatomically characterized number of ipRGCs). This relatively widespread response dissipated with repeated stimulation even at a quite long inter-stimulus interval (ISI; 120 s), to leave a smaller fraction of responsive units (<10%; more in tune with the predicted number of ipRGCs). Visually intact retinas appeared to lack such widespread melanopsin responses indicating that it is a feature of dystrophy. Taken together, our data reveal the potential for anomalously widespread melanopsin responses in advanced retinal degeneration. These could be used to probe the functional reorganization of retinal circuits in degeneration and should be taken into account when using retinally degenerate mice as a model of disease.
This paper identifies and describes measures of constructs relevant to the adoption or implementation of innovations (i.e., new policies, programs or practices) at the organizational-level. This work ...is intended to advance the field of dissemination and implementation research by aiding scientists in the identification of existing measures and highlighting methodological issues that require additional attention.
We searched for published studies (1973-2013) in 11 bibliographic databases for quantitative, empirical studies that presented outcome data related to adoption and/or implementation of an innovation. Included studies had to assess latent constructs related to the "inner setting" of the organization, as defined by the Consolidated Framework for Implementation Research.
Of the 76 studies included, most (86%) were cross sectional and nearly half (49%) were conducted in health care settings. Nearly half (46%) involved implementation of evidence-based or "best practice" strategies; roughly a quarter (26%) examined use of new technologies. Primary outcomes most often assessed were innovation implementation (57%) and adoption (34%); while 4% of included studies assessed both outcomes. There was wide variability in conceptual and operational definitions of organizational constructs. The two most frequently assessed constructs included "organizational climate" and "readiness for implementation." More than half (55%) of the studies did not articulate an organizational theory or conceptual framework guiding the inquiry; about a third (34%) referenced Diffusion of Innovations theory. Overall, only 46% of articles reported psychometric properties of measures assessing latent organizational characteristics. Of these, 94% (33/35) described reliability and 71% (25/35) reported on validity.
The lack of clarity associated with construct definitions, inconsistent use of theory, absence of standardized reporting criteria for implementation research, and the fact that few measures have demonstrated reliability or validity were among the limitations highlighted in our review. Given these findings, we recommend that increased attention be devoted toward the development or refinement of measures using common psychometric standards. In addition, there is a need for measure development and testing across diverse settings, among diverse population samples, and for a variety of types of innovations.
An animal's temporal niche - the time of day at which it is active - is known to drive a variety of adaptations in the visual system. These include variations in the topography, spectral sensitivity ...and density of retinal photoreceptors, and changes in the eye's gross anatomy and spectral transmission characteristics. We have characterised visual spectral sensitivity in the murid rodent
(the four-striped grass mouse), which is in the same family as (nocturnal) mice and rats but exhibits a strong diurnal niche. As is common in diurnal species, the
lens acts as a long-pass spectral filter, providing limited transmission of light <400 nm. Conversely, we found strong sequence homologies with the
SWS and MWS opsins and those of related nocturnal species (mice and rats) whose SWS opsins are maximally sensitive in the near-UV. We continued to assess
spectral sensitivity of cone vision using electroretinography and multi-channel recordings from the visual thalamus. These revealed that responses across the human visible range could be adequately described by those of a single pigment (assumed to be MWS opsin) maximally sensitive at ∼500 nm, but that sensitivity in the near-UV required inclusion of a second pigment whose peak sensitivity lay well into the UV range (λ
<400 nm, probably ∼360 nm). We therefore conclude that, despite the UV-filtering effects of the lens,
retains an SWS pigment with a UV-A λ
In effect, this somewhat paradoxical combination of long-pass lens and UV-A λ
results in narrow-band sensitivity for SWS cone pathways in the UV-A range.
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