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Article: Colour and melanopsin mediated responses in the murine retina.

Mouland, Joshua W / Watson, Alex J / Martial, Franck P / Lucas, Robert J / Brown, Timothy M

2023 Volume 17, Page(s) 1114634

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-03-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2023.1114634
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Article ; Online: Modulations in irradiance directed at melanopsin, but not cone photoreceptors, reliably alter electrophysiological activity in the suprachiasmatic nucleus and circadian behaviour in mice.

Mouland, Josh W / Martial, Franck P / Lucas, Robert J / Brown, Timothy M

Journal of pineal research

2021 Volume 70, Issue 4, Page(s) e12735

Abstract: Intrinsically photosensitive retinal ganglion cells convey intrinsic, melanopsin-based, photoreceptive signals alongside those produced by rods and cones to the suprachiasmatic nucleus (SCN) circadian clock. To date, experimental data suggest that ... ...

Abstract	Intrinsically photosensitive retinal ganglion cells convey intrinsic, melanopsin-based, photoreceptive signals alongside those produced by rods and cones to the suprachiasmatic nucleus (SCN) circadian clock. To date, experimental data suggest that melanopsin plays a more significant role in measuring ambient light intensity than cone photoreception. Such studies have overwhelmingly used diffuse light stimuli, whereas light intensity in the world around us varies across space and time. Here, we investigated the extent to which melanopsin or cone signals support circadian irradiance measurements in the presence of naturalistic spatiotemporal variations in light intensity. To address this, we first presented high- and low-contrast movies to anaesthetised mice whilst recording extracellular electrophysiological activity from the SCN. Using a mouse line with altered cone sensitivity (Opn1mw
MeSH term(s)	Animals ; Behavior, Animal/radiation effects ; Circadian Rhythm/physiology ; Circadian Rhythm/radiation effects ; Humans ; Light/adverse effects ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Retinal Cone Photoreceptor Cells/radiation effects ; Rod Opsins/radiation effects ; Suprachiasmatic Nucleus/physiology
Chemical Substances	Rod Opsins ; melanopsin
Language	English
Publishing date	2021-04-01
Publishing country	England
Document type	Journal Article
ZDB-ID	632697-3
ISSN	1600-079X ; 0742-3098
ISSN (online)	1600-079X
ISSN	0742-3098
DOI	10.1111/jpi.12735
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Article ; Online: Three-dimensional unsupervised probabilistic pose reconstruction (3D-UPPER) for freely moving animals.

Ebrahimi, Aghileh S / Orlowska-Feuer, Patrycja / Huang, Qian / Zippo, Antonio G / Martial, Franck P / Petersen, Rasmus S / Storchi, Riccardo

Scientific reports

2023 Volume 13, Issue 1, Page(s) 155

Abstract: A key step in understanding animal behaviour relies in the ability to quantify poses and movements. Methods to track body landmarks in 2D have made great progress over the last few years but accurate 3D reconstruction of freely moving animals still ... ...

Abstract	A key step in understanding animal behaviour relies in the ability to quantify poses and movements. Methods to track body landmarks in 2D have made great progress over the last few years but accurate 3D reconstruction of freely moving animals still represents a challenge. To address this challenge here we develop the 3D-UPPER algorithm, which is fully automated, requires no a priori knowledge of the properties of the body and can also be applied to 2D data. We find that 3D-UPPER reduces by [Formula: see text] fold the error in 3D reconstruction of mouse body during freely moving behaviour compared with the traditional triangulation of 2D data. To achieve that, 3D-UPPER performs an unsupervised estimation of a Statistical Shape Model (SSM) and uses this model to constrain the viable 3D coordinates. We show, by using simulated data, that our SSM estimator is robust even in datasets containing up to 50% of poses with outliers and/or missing data. In simulated and real data SSM estimation converges rapidly, capturing behaviourally relevant changes in body shape associated with exploratory behaviours (e.g. with rearing and changes in body orientation). Altogether 3D-UPPER represents a simple tool to minimise errors in 3D reconstruction while capturing meaningful behavioural parameters.
MeSH term(s)	Animals ; Mice ; Imaging, Three-Dimensional/methods ; Algorithms ; Movement ; Behavior, Animal
Language	English
Publishing date	2023-01-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-25087-4
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Article ; Online: Modulating signalling lifetime to optimise a prototypical animal opsin for optogenetic applications.

Rodgers, Jessica / Wright, Phillip / Ballister, Edward R / Hughes, Rebecca B / Storchi, Riccardo / Wynne, Jonathan / Martial, Franck P / Lucas, Robert J

Pflugers Archiv : European journal of physiology

2023 Volume 475, Issue 12, Page(s) 1387–1407

Abstract: Animal opsins are light activated G-protein-coupled receptors, capable of optogenetic control of G-protein signalling for research or therapeutic applications. Animal opsins offer excellent photosensitivity, but their temporal resolution can be limited ... ...

Abstract	Animal opsins are light activated G-protein-coupled receptors, capable of optogenetic control of G-protein signalling for research or therapeutic applications. Animal opsins offer excellent photosensitivity, but their temporal resolution can be limited by long photoresponse duration when expressed outside their native cellular environment. Here, we explore methods for addressing this limitation for a prototypical animal opsin (human rod opsin) in HEK293T cells. We find that the application of the canonical rhodopsin kinase (GRK1)/visual arrestin signal termination mechanism to this problem is complicated by a generalised suppressive effect of GRK1 expression. This attenuation can be overcome using phosphorylation-independent mutants of arrestin, especially when these are tethered to the opsin protein. We further show that point mutations targeting the Schiff base stability of the opsin can also reduce signalling lifetime. Finally, we apply one such mutation (E122Q) to improve the temporal fidelity of restored visual responses following ectopic opsin expression in the inner retina of a mouse model of retinal degeneration (rd1). Our results reveal that these two strategies (targeting either arrestin binding or Schiff-base hydrolysis) can produce more time-delimited opsin signalling under heterologous expression and establish the potential of this approach to improve optogenetic performance.
MeSH term(s)	Animals ; Mice ; Humans ; Rod Opsins/genetics ; Rod Opsins/metabolism ; Opsins/genetics ; Opsins/metabolism ; Optogenetics/methods ; HEK293 Cells ; Arrestins/genetics ; Arrestins/metabolism
Chemical Substances	Rod Opsins ; Opsins ; Arrestins
Language	English
Publishing date	2023-12-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-023-02879-9
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Article ; Online: The mouse suprachiasmatic nucleus encodes irradiance via a diverse population of neurons monotonically tuned to different ranges of intensity.

Orlowska-Feuer, Patrycja / Bano-Otalora, Beatriz / Rodgers, Jessica / Martial, Franck P / Storchi, Riccardo / Lucas, Robert James

The Journal of physiology

2023 Volume 601, Issue 21, Page(s) 4737–4749

Abstract: Many neurons of the mammalian master circadian oscillator in the suprachiasmatic nuclei (SCN) respond to light pulses with irradiance-dependent changes in firing. Here, we set out to better understand this irradiance coding ability by considering how the ...

Abstract	Many neurons of the mammalian master circadian oscillator in the suprachiasmatic nuclei (SCN) respond to light pulses with irradiance-dependent changes in firing. Here, we set out to better understand this irradiance coding ability by considering how the SCN tracks more continuous changes in irradiance at both population and single unit level. To this end, we recorded extracellular activity in the SCN of anaesthetised mice presented with up + down irradiance staircase stimuli covering moonlight to daylight conditions and incorporating epochs with steady light or superimposed higher frequency modulations (temporal white noise (WN) and frequency/contrast chirps). Single unit activity was extracted by spike sorting. The population response of SCN units to this stimulus was a progressive increase in firing rate at higher irradiances. This relationship was symmetrical for up vs. down phases of the ramp in the presence of white noise or chirps but exhibited hysteresis for steady light, with firing systematically higher during increasing irradiance. Single units also showed a monotonic relationship between firing and irradiance but exhibited diversity not only in response polarity (increases vs. decreases in firing), but also in the sensitivity (EC
MeSH term(s)	Mice ; Animals ; Circadian Rhythm/physiology ; Suprachiasmatic Nucleus/physiology ; Neurons/physiology ; Light ; Circadian Clocks ; Mammals
Language	English
Publishing date	2023-10-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP285000
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Article ; Online: Form vision from melanopsin in humans.

Allen, Annette E / Martial, Franck P / Lucas, Robert J

Nature communications

2019 Volume 10, Issue 1, Page(s) 2274

Abstract: Detection and discrimination of spatial patterns is thought to originate with photoreception by rods and cones. Here, we investigated whether the inner-retinal photoreceptor melanopsin could represent a third origin for form vision. We developed a 4- ... ...

Abstract	Detection and discrimination of spatial patterns is thought to originate with photoreception by rods and cones. Here, we investigated whether the inner-retinal photoreceptor melanopsin could represent a third origin for form vision. We developed a 4-primary visual display capable of presenting patterns differing in contrast for melanopsin vs cones, and generated spectrally distinct stimuli that were indistinguishable for cones (metamers) but presented contrast for melanopsin. Healthy observers could detect sinusoidal gratings formed by these metamers when presented in the peripheral retina at low spatial (≤0.8 cpd) and temporal (≤0.45 Hz) frequencies, and Michelson contrasts ≥14% for melanopsin. Metameric gratings became invisible at lower light levels (<10
MeSH term(s)	Female ; Form Perception/physiology ; Healthy Volunteers ; Humans ; Male ; Retinal Cone Photoreceptor Cells/physiology ; Rod Opsins/physiology ; Vision, Ocular/physiology
Chemical Substances	Rod Opsins ; melanopsin
Language	English
Publishing date	2019-05-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-019-10113-3
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Article ; Online: Visual responses in the dorsal lateral geniculate nucleus at early stages of retinal degeneration in

Procyk, Christopher A / Allen, Annette E / Martial, Franck P / Lucas, Robert J

Journal of neurophysiology

2019 Volume 122, Issue 4, Page(s) 1753–1764

Abstract: Inherited retinal degenerations encompass a wide range of diseases that result in the death of rod and cone photoreceptors, eventually leading to irreversible blindness. Low vision survives at early stages of degeneration, at which point it could rely on ...

Abstract	Inherited retinal degenerations encompass a wide range of diseases that result in the death of rod and cone photoreceptors, eventually leading to irreversible blindness. Low vision survives at early stages of degeneration, at which point it could rely on residual populations of rod/cone photoreceptors as well as the inner retinal photoreceptor, melanopsin. To date, the impact of partial retinal degeneration on visual responses in the primary visual thalamus (dorsal lateral geniculate nucleus, dLGN) remains unknown, as does their relative reliance on surviving rod and cone photoreceptors vs. melanopsin. To answer these questions, we recorded visually evoked responses in the dLGN of anesthetized
MeSH term(s)	Animals ; Contrast Sensitivity ; Cyclic Nucleotide Phosphodiesterases, Type 6/genetics ; Evoked Potentials, Visual ; Gamma Rhythm ; Geniculate Bodies/physiopathology ; Mice ; Mice, Inbred C57BL ; Reaction Time ; Retinal Cone Photoreceptor Cells/pathology ; Retinal Cone Photoreceptor Cells/physiology ; Retinal Degeneration/genetics ; Retinal Degeneration/physiopathology ; Retinal Rod Photoreceptor Cells/pathology ; Retinal Rod Photoreceptor Cells/physiology ; Vision, Ocular
Chemical Substances	Cyclic Nucleotide Phosphodiesterases, Type 6 (EC 3.1.4.35)
Language	English
Publishing date	2019-08-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00231.2019
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Article: Melanopsin Driven Light Responses Across a Large Fraction of Retinal Ganglion Cells in a Dystrophic Retina.

Eleftheriou, Cyril G / Wright, Phillip / Allen, Annette E / Elijah, Daniel / Martial, Franck P / Lucas, Robert J

Frontiers in neuroscience

2020 Volume 14, Page(s) 320

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2020-04-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2020.00320
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Article ; Online: Optogenetic manipulation of BMP signaling to drive chondrogenic differentiation of hPSCs.

Humphreys, Paul E A / Woods, Steven / Bates, Nicola / Rooney, Kirsty M / Mancini, Fabrizio E / Barclay, Cerys / O'Flaherty, Julieta / Martial, Franck P / Domingos, Marco A N / Kimber, Susan J

Cell reports

2023 Volume 42, Issue 12, Page(s) 113502

Abstract: Optogenetics is a rapidly advancing technology combining photochemical, optical, and synthetic biology to control cellular behavior. Together, sensitive light-responsive optogenetic tools and human pluripotent stem cell differentiation models have the ... ...

Abstract	Optogenetics is a rapidly advancing technology combining photochemical, optical, and synthetic biology to control cellular behavior. Together, sensitive light-responsive optogenetic tools and human pluripotent stem cell differentiation models have the potential to fine-tune differentiation and unpick the processes by which cell specification and tissue patterning are controlled by morphogens. We used an optogenetic bone morphogenetic protein (BMP) signaling system (optoBMP) to drive chondrogenic differentiation of human embryonic stem cells (hESCs). We engineered light-sensitive hESCs through CRISPR-Cas9-mediated integration of the optoBMP system into the AAVS1 locus. The activation of optoBMP with blue light, in lieu of BMP growth factors, resulted in the activation of BMP signaling mechanisms and upregulation of a chondrogenic phenotype, with significant transcriptional differences compared to cells in the dark. Furthermore, cells differentiated with light could form chondrogenic pellets consisting of a hyaline-like cartilaginous matrix. Our findings indicate the applicability of optogenetics for understanding human development and tissue engineering.
MeSH term(s)	Humans ; Optogenetics ; Chondrocytes ; Cell Differentiation/genetics ; Cartilage/metabolism ; Pluripotent Stem Cells ; Chondrogenesis/genetics ; Bone Morphogenetic Protein 2/metabolism ; Cells, Cultured
Chemical Substances	Bone Morphogenetic Protein 2
Language	English
Publishing date	2023-11-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.113502
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Article ; Online: Pupil responses to hidden photoreceptor-specific modulations in movies.

Spitschan, Manuel / Gardasevic, Marina / Martial, Franck P / Lucas, Robert J / Allen, Annette E

PloS one

2019 Volume 14, Issue 5, Page(s) e0216307

Abstract: Under typical daytime light levels, the human pupillary light response (PLR) is driven by the activity of the L, M, and S cones, and melanopsin expressed in the so-called intrinsically photosensitive retinal ganglion cells (ipRGCs). However, the ... ...

Abstract	Under typical daytime light levels, the human pupillary light response (PLR) is driven by the activity of the L, M, and S cones, and melanopsin expressed in the so-called intrinsically photosensitive retinal ganglion cells (ipRGCs). However, the importance of each of these photoreceptive mechanisms in defining pupil size under real-world viewing conditions remains to be established. To address this question, we embedded photoreceptor-specific modulations in a movie displayed using a novel projector-based five-primary spatial stimulation system, which allowed for the precise control of photoreceptor activations in time and space. We measured the pupillary light response in eleven observers, who viewed short cartoon movies which contained hidden low-frequency (0.25 Hz) silent-substitution modulations of the L, M and S cones (no stimulation of melanopsin), melanopsin (no stimulation of L, M and S cones), both L, M, and S cones and melanopsin or no modulation at all. We find that all photoreceptors active at photopic light levels regulate pupil size under this condition. Our data imply that embedding modulations in photoreceptor contrast could provide a method to manipulate key adaptive aspects of the human visual system in everyday, real-world activities such as watching a movie.
MeSH term(s)	Adult ; Female ; Humans ; Male ; Motion Pictures ; Photic Stimulation ; Pupil/physiology ; Reflex, Pupillary/physiology ; Retinal Cone Photoreceptor Cells/physiology ; Retinal Rod Photoreceptor Cells/physiology
Language	English
Publishing date	2019-05-09
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0216307
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