In mammals, a small number of retinal ganglion cells express melanopsin, an opsin photopigment, allowing them to be directly photoreceptive. A major function of these so-called intrinsically ...photosensitive retinal ganglion cells (ipRGCs) is to synchronize (entrain) endogenous circadian clocks to the external light:dark cycle. Thanks to their intrinsic light response, ipRGCs can support photoentrainment even when the other retinal photoreceptors (rods and cones) are absent or inactive. However, in the intact retina the ipRGC light response is a composite of extrinsic (rod/cone) and intrinsic (melanopsin) influences. As a result all three photoreceptor classes contribute to the retinal pathways providing light information to the clock. Here, we consider what each photoreceptor type contributes to the clock light response. We review electrophysiological and behavioral data pertinent to this question, primarily from laboratory rodents, drawing them together to provide a conceptual model in which each photoreceptor class plays a distinct role in encoding the light environment. We finally use this model to highlight some of the important outstanding questions in this field.
Retinal dopamine is released by a specialized subset of amacrine cells in response to light and has a potent influence on how the retina responds to, and encodes, visual information. Here, we address ...the critical question of which retinal photoreceptor is responsible for coordinating the release of this neuromodulator. Although all three photoreceptor classes—rods, cones, and melanopsin-containing retinal ganglion cells (mRGCs)—have been shown to provide electrophysiological inputs to dopaminergic amacrine cells (DACs), we show here that the release of dopamine is defined only by rod photoreceptors. Remarkably, this rod signal coordinates both a suppressive signal at low intensities and drives dopamine release at very bright light intensities. These data further reveal that dopamine release does not necessarily correlate with electrophysiological activity of DACs and add to a growing body of evidence that rods define aspects of retinal function at very bright light levels.
•Rod activation alone mediates light-dependent retinal dopamine release•Rod-driven light-induced dopamine release is confined to photopic light levels•Rods suppress dopamine release under scotopic and mesopic light conditions•Spiking activity of dopaminergic amacrines is not correlated with dopamine release
Pérez-Fernández et al. find that light-induced dopamine release in the mouse retina is defined by rod photoreceptor activation. Stimulation under dim to mesopic light intensities causes dopamine release to be suppressed, and bright photopic light intensities cause extensive dopamine release.
The discovery of melanopsin as a third type of retinal photoreceptor, contributing to both perceptual vision and reflex light responses, represents a new opportunity to optimise the design of ...artificial light sources for practical applications and to generate experimental stimuli. In the case of emissive displays, multiprimary designs incorporating a cyan primary could be used to allow melanopic radiance to be controlled independent of colour and luminance. Here we explore the performance a five-primary (violet, cyan, green, yellow, red) display device and find an anomaly in colour appearance when the cyan primary is employed. The anomaly took the form of a reddish/pinkish tinge in the central visual field, consistent with descriptions of Maxwell’s spot. This effect was apparent in some full colour images and in uniform discs over a range of chromaticities. Its appearance in coloured discs correlated with differences in calculated colour coordinate between central and peripheral vision. A simulation indicated that inclusion of any primary with predominant output in the 470–500 nm range has the potential to produce such a discrepancy in central vs peripheral appearance. Applying an additional constraint in colour processing to reproduce naturally occurring differences in central vs peripheral colour coordinate eliminated appearance of the spot and produced acceptable colour images.
Key points
The lateral posterior and posterior thalamic nuclei have been implicated in aspects of visually guided behaviour and reflex responses to light, including those dependent on melanopsin ...photoreception.
Here we investigated the extent and basic properties of visually evoked activity across the mouse lateral posterior and posterior thalamus.
We show that a subset of retinal projections to these regions derive from melanopsin‐expressing retinal ganglion cells and find many cells that exhibit melanopsin‐dependent changes in firing.
We also show that subsets of cells across these regions integrate signals from both eyes in various ways and that, within the lateral posterior thalamus, visual responses are retinotopically ordered.
In addition to the primary thalamocortical visual relay in the lateral geniculate nuclei, a number of other thalamic regions contribute to aspects of visual processing. Thus, the lateral posterior thalamic nuclei (LP/pulvinar) appear important for various functions including determining visual saliency, visually guided behaviours and, alongside dorsal portions of the posterior thalamic nuclei (Po), multisensory processing of information related to aversive stimuli. However, despite the growing importance of mice as a model for understanding visual system organisation, at present we know very little about the basic visual response properties of cells in the mouse LP or Po. Prompted by earlier suggestions that melanopsin photoreception might be important for certain functions of these nuclei, we first employ specific viral tracing to show that a subset of retinal projections to the LP derive from melanopsin‐expressing retinal ganglion cells. We next use multielectrode electrophysiology to demonstrate that LP and dorsal Po cells exhibit a variety of responses to simple visual stimuli including two distinct classes that express melanopsin‐dependent changes in firing (together comprising ∼25% of neurons we recorded). We also show that subgroups of LP/Po cells integrate signals from both eyes in various ways and that, within the LP, visual responses are retinotopically ordered. Together our data reveal a diverse population of visually responsive neurons across the LP and dorsal Po whose properties align with some of the established functions of these nuclei and suggest new possible routes through which melanopsin photoreception could contribute to reflex light responses and/or higher order visual processing.
Key points
The lateral posterior and posterior thalamic nuclei have been implicated in aspects of visually guided behaviour and reflex responses to light, including those dependent on melanopsin photoreception.
Here we investigated the extent and basic properties of visually evoked activity across the mouse lateral posterior and posterior thalamus.
We show that a subset of retinal projections to these regions derive from melanopsin‐expressing retinal ganglion cells and find many cells that exhibit melanopsin‐dependent changes in firing.
We also show that subsets of cells across these regions integrate signals from both eyes in various ways and that, within the lateral posterior thalamus, visual responses are retinotopically ordered.
Intrinsically photosensitive retinal ganglion cells (ipRGCs) are photoreceptors located in the ganglion cell layer. They project to brain regions involved in predominately non-image-forming functions ...including entrainment of circadian rhythms, control of the pupil light reflex, and modulation of mood and behavior. In addition to possessing intrinsic photosensitivity via the photopigment melanopsin, these cells receive inputs originating in rods and cones. While most research in the last two decades has focused on the downstream influence of ipRGC signaling, recent studies have shown that ipRGCs also act retrogradely within the retina itself as intraretinal signaling neurons. In this article, we review studies examining intraretinal and, in addition, intraocular signaling pathways of ipRGCs. Through these pathways, ipRGCs regulate inner and outer retinal circuitry through both chemical and electrical synapses, modulate the outputs of ganglion cells (both ipRGCs and non-ipRGCs), and influence arrangement of the correct retinal circuitry and vasculature during development. These data suggest that ipRGC function plays a significant role in the processing of image-forming vision at its earliest stage, positioning these photoreceptors to exert a vital role in perceptual vision. This research will have important implications for lighting design to optimize the best chromatic lighting environments for humans, both in adults and potentially even during fetal and postnatal development. Further studies into these unique ipRGC signaling pathways could also lead to a better understanding of the development of ocular dysfunctions such as myopia.
The designer stimulant 4-methylmethcathinone (mephedrone) is among the most popular of the derivatives of the naturally occurring psychostimulant cathinone. Mephedrone has been readily available for ...legal purchase both online and in some stores and has been promoted by aggressive Web-based marketing. Its abuse in many countries, including the United States, is a serious public health concern. Owing largely to its recent emergence, there are no formal pharmacodynamic or pharmacokinetic studies of mephedrone. Accordingly, the purpose of this study was to evaluate effects of this agent in a rat model. Results revealed that, similar to methylenedioxymethamphetamine, methamphetamine, and methcathinone, repeated mephedrone injections (4× 10 or 25 mg/kg s.c. per injection, 2-h intervals, administered in a pattern used frequently to mimic psychostimulant "binge" treatment) cause a rapid decrease in striatal dopamine (DA) and hippocampal serotonin (5-hydroxytryptamine; 5HT) transporter function. Mephedrone also inhibited both synaptosomal DA and 5HT uptake. Like methylenedioxymethamphetamine, but unlike methamphetamine or methcathinone, repeated mephedrone administrations also caused persistent serotonergic, but not dopaminergic, deficits. However, mephedrone caused DA release from a striatal suspension approaching that of methamphetamine and was self-administered by rodents. A method was developed to assess mephedrone concentrations in rat brain and plasma, and mephedrone levels were determined 1 h after a binge treatment. These data demonstrate that mephedrone has a unique pharmacological profile with both abuse liability and neurotoxic potential.
In addition to rods and cones, photoreception in mammals extends to a third retinal cell type expressing the photopigment melanopsin. The influences of this novel opsin are widespread, ranging from ...pupillary and circadian responses to brightness perception, yet established approaches to quantifying the biological effects of light do not adequately account for melanopsin sensitivity. We have recently proposed a novel metric, the melanopic sensitivity function (V(Z)λ), to address this deficiency. Here, we further validate this new measure with a variety of tests based on potential barriers to its applicability identified in the literature or relating to obvious practical benefits. Using electrophysiogical approaches and pupillometry, initially in rodless+coneless mice, our data demonstrate that under a very wide range of different conditions (including switching between stimuli with highly divergent spectral content) the V(Z)λ function provides an accurate prediction of the sensitivity of melanopsin-dependent responses. We further show that V(Z)λ provides the best available description of the spectral sensitivity of at least one aspect of the visual response in mice with functional rods and cones: tonic firing activity in the lateral geniculate nuclei. Together, these data establish V(Z)λ as an important new approach for light measurement with widespread practical utility.
There is no consensus on the best inhibitory optogenetic tool. Since Gi/o signalling is a native mechanism of neuronal inhibition, we asked whether Lamprey Parapinopsin (“Lamplight”), a Gi/o‐coupled ...bistable animal opsin, could be used for optogenetic silencing. We show that short (405 nm) and long (525 nm) wavelength pulses repeatedly switch Lamplight between stable signalling active and inactive states, respectively, and that combining these wavelengths can be used to achieve intermediate levels of activity. These properties can be applied to produce switchable neuronal hyperpolarisation and suppression of spontaneous spike firing in the mouse hypothalamic suprachiasmatic nucleus. Expressing Lamplight in (predominantly) ON bipolar cells can photosensitise retinas following advanced photoreceptor degeneration, with 405 and 525 nm stimuli producing responses of opposite sign in the output neurons of the retina. We conclude that bistable animal opsins can co‐opt endogenous signalling mechanisms to allow optogenetic inhibition that is scalable, sustained and reversible.
SYNOPSIS
Lamprey parapinopsin is a Gi/o‐coupled bistable animal opsin activated and deactivated by short and long wavelength light, respectively. This study shows that Lamplight can be used as a reversible inhibitory optogenetic tool in mice.
Lamplight can produce reversible hyperpolarisation in brain neurons and photoswitchable changes in the retina.
Single light pulses can produce sustained inhibition.
Lamplight‐driven Go activity can be controlled by modulating either the intensity or the spectral composition of the light stimulus.
Lamprey parapinopsin is a Gi/o‐coupled bistable animal opsin activated and deactivated by short and long wavelength light, respectively. This study shows that Lamplight can be used as a reversible inhibitory optogenetic tool in mice.
Key points
Using in vivo electrophysiology, we find that a subset of whisker‐responsive neurons in the ventral posterior medial region (VPM) respond to visual stimuli.
These light‐responsive neurons ...in the VPM are particularly sensitive to optic flow.
Presentation of optic flow stimuli modulates the amplitude of concurrent whisker responses.
Visual information reaches the VPM via a circuit encompassing the visual cortex.
These data represent a new example of cross‐modal integration in the primary sensory thalamus.
Sensory signals reach the cortex via sense‐specific thalamic nuclei. Here we report that neurons in the primary sensory thalamus of the mouse vibrissal system (the ventral posterior medial region; VPM) can be excited by visual as well as whisker stimuli. Using extracellular electrophysiological recordings from anaesthetized mice we first show that simple light steps can excite a subset of VPM neurons. We then test the ability of the VPM to respond to spatial patterns and show that many units are excited by visual motion in a direction‐selective manner. Coherent movement of multiple objects (an artificial recreation of ‘optic flow’ that would usually occur during head rotations or body movements) best engages this visual motion response. We next show that, when co‐applied with visual stimuli, the magnitude of responses to whisker deflections is highest in the presence of optic flow going in the opposite direction. Importantly, whisker response amplitude is also modulated by presentation of a movie recreating the mouse's visual experience during natural exploratory behaviour. We finally present functional and anatomical data indicating a functional connection (probably multisynaptic) from the primary visual cortex to VPM. These data provide a rare example of multisensory integration occurring at the level of the sensory thalamus, and provide evidence for dynamic regulation of whisker responses according to visual experience.
Key points
Using in vivo electrophysiology, we find that a subset of whisker‐responsive neurons in the ventral posterior medial region (VPM) respond to visual stimuli.
These light‐responsive neurons in the VPM are particularly sensitive to optic flow.
Presentation of optic flow stimuli modulates the amplitude of concurrent whisker responses.
Visual information reaches the VPM via a circuit encompassing the visual cortex.
These data represent a new example of cross‐modal integration in the primary sensory thalamus.
Circadian rhythms in the blind Allen, Annette E
Current opinion in behavioral sciences,
December 2019, 2019-12-00, Letnik:
30
Journal Article
Recenzirano
•The circadian clock is a critical modulator of human physiology and behaviour.•Light is the most important cue for entraining the clock with the environment.•Blindness often leads to an inability to ...entrain the clock with external time.•Melanopsin photoreceptors can allow entrainment in the absence of visual perception.
Light has a profound influence on human physiology and behaviour, most notably permitting visual perception. However, light information serves a parallel set of functions in biology that are essential for our health and wellbeing, including the synchronisation of our circadian clock to the solar day. The circadian clock drives endogenous daily rhythms across human physiology and behaviour. However, when the circadian clock is not appropriately aligned with external time, disturbances in sleep/wake behaviours, alertness, mood and performance arise. Here, the important question of how blindness — a loss of visual perception — impacts the circadian clock’s synchronisation with the solar day is discussed. This review will explore how and why vision loss can cause significant disruptions in behaviour and physiology that go beyond the loss of conscious visual perception, and why blindness is not as closely linked with deficits in photoentrainment as we might expect.
PDF
