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  • Immunocytochemical studies on the LHRH system of the Japanese quail: influence by photoperiod and aspects of sexual differentiation.

    27 November 2018

    Immunocytochemistry was used to determine if photoperiod and/or sex have any effect on the pattern of the luteinizing hormone-releasing hormone (LHRH) system in the brain of the Japanese quail. Immunopositive perikarya were found within three major areas of the brain: the rostral paraolfactory lobe, the preoptic, and the septal region. A quantitative analysis of LHRH cell numbers was performed on male and female quail after two photoperiodic treatments: sexually mature birds exposed to 24 weeks of 20 h light: 4 h darkness (20L:4D), and birds with a regressed reproductive system (induced by transfer from a photoregime of 20L:4D to 25 short days of 8L:16D). Two-way analysis of variance showed that short-day males display significantly (p less than 0.05) more immunopositive perikarya (607 +/- 134) than long-day males (291 +/- 114), short-day females (293 +/- 103) or long-day females (330 +/- 92). The density of LHRH-immunoreactive nerve fibres and the intensity of the immunostaining in the median eminence were always greater in long-day sexually mature quail (male and female) than in animals exposed to 25 days of 8L:16D. These results demonstrate that the LHRH system of the quail is influenced by photoperiod and mirrors sexual differentiation.

  • Evidence for a daily rhythmicity in the acute release of luteinizing hormone in response to electrical stimulation in the Japanese quail.

    27 November 2018

    This study was undertaken to examine the effect of electrical stimulation of the hypothalamus at different times of day on luteinizing hormone (LH) secretion in male castrated quail on short days (8L:16D). The posterior hypothalamus was stimulated with square-wave pulses of 80 microA for 2 min through chronically-implanted platinum microelectrodes. Stimulation was carried out on each quail at 4 (treatment A), 10 (B), or 14 h (C) after dawn. Plasma LH levels were increased markedly within 2 min of ending the stimulation but reached basal levels again over the next 20 min or so. The absolute increase was significantly greater in treatment B (10 h after lights on) than at the other times tested. This is consistent with a rhythm in hypothalamic responsivity. The results are discussed in the context of the rhythm of photoinducibility which occurs early in the night and which is used by quail as a photoperiodic clock to regulate seasonal reproduction.

  • Opsins and mammalian photoentrainment.

    27 November 2018

    Research over the past decade has provided overwhelming evidence that photoreception in the vertebrate eye is not confined to the rod and cone photoreceptors. It appears that photoreceptor cells within the inner retina provide irradiance information to a wide variety of different photosensory tasks including photoentrainment, pupillary constriction and masking behaviour. Action spectra in mice lacking all rod and cone photoreceptors ( rd/rd cl) have demonstrated the existence of a previously uncharacterised, opsin/vitamin-A-based photopigment with peak sensitivity at 479 nm (opsin photopigment/OP(479)). The review addresses the question: has the gene encoding OP(479) already been isolated, and if not, what type of gene should we be seeking and where in the eye might this gene be expressed? On the basis of available data, the gene that encodes OP(479) remains unidentified, and two broad possibilities exist. On the assumption that OP(479) will be like all of the other vertebrate photopigments (ocular and extraocular) and share a close phylogenetic relationship based upon amino acid identity and a conserved genomic structure, then the gene encoding OP(479) has yet to be isolated. Alternatively, there may have been a separate line of photopigment evolution in the vertebrates that has given rise to the melanopsin family. If true then the mammalian melanopsin gene may encode OP(479). Only when melanopsin and other candidates for OP(479) have been functionally expressed, and shown to encode a photopigment that matches the action spectrum of OP(479), can firm conclusions about the identity of the non-rod, non-cone ocular photoreceptor of mammals be made.

  • Visual and circadian responses to light in aged retinally degenerate mice.

    27 November 2018

    The progression of photoreceptor degeneration in retinally degenerate (rd) mice commences early in postnatal development resulting in the complete loss of rods by 60-70 days of age followed by the more protracted loss of cones. We have previously shown that rd mice 80 days of age are capable of phase shifting their circadian locomotor rhythms in response to brief pulses of light and these animals show the same sensitivity as wild-type (+/+) controls. If surviving cones mediate these circadian responses, then one would expect the sensitivity of the circadian system in rd mice to decline with age and parallel the loss of cones. We demonstrate that aging rd mice (80-767 days of age) remain capable of photically regulating circadian locomotor rhythms in a manner indistinguishable from +/+ mice. Circadian responses to light do not parallel cone cell degeneration in rd mice. In contrast to the circadian responses to light, old (> 210 days of age) rd mice show no visually-evoked behavioral or electroretinogram (ERG) responses.

  • Circadian photoreception in the retinally degenerate mouse (rd/rd).

    27 November 2018

    We have examined the effects of light on circadian locomotor rhythms in retinally degenerate mice (C57BL/6J mice homozygous for the rd allele: rd/rd). The sensitivity of circadian photoreception in these mice was determined by varying the irradiance of a 15 min light pulse (515 nm) given at circadian time 16 and measuring the magnitude of the phase shift of the locomotor rhythm. Experiments were performed on animals 80 days of age. Despite the loss of visual photoreceptors in the rd/rd retina, animals showed circadian responses to light that were indistinguishable from mice with normal retinas (rd/+ and +/+). While no photoreceptor outersegments were identified in the retina of rd/rd animals (80-100 days of age), we did identify a small number of perikarya that were immunoreactive for cone opsins, and even fewer cells that contained rod opsin. Using HPLC, we demonstrated the presence and photoisomerization of the rhodopsin chromophore 11-cis retinaldehyde. The rd/rd retinas contained about 2% of 11-cis retinaldehyde found in +/+ retinas. We have yet to determine whether the opsin immunoreactive perikarya or some other unidentified cell type mediate circadian light detection in the rd/rd retina.

  • Absence of phosphoglucose isomerase-1 in retinal photoreceptor, pigment epithelium and Muller cells.

    27 November 2018

    Macroarray analysis was used to compare equal amounts of cDNA from wild-type and rd/rd (retinal degeneration) mice, collected at P90 when photoreceptor degeneration is virtually complete. A stronger signal for the glycolytic enzyme phosphoglucose isomerase (Gpi1) was observed in the rd/rd sample. Extracellularly, Gpi1 may act as a cytokine, independently described as neuroleukin and autocrine motility factor. Retinal Gpi1 expression was investigated by Northern and Western blot analysis and immunohistochemistry. Double-labelling was performed with antibodies against Gpi1 and calbindin-D, glutamine synthetase, RPE65, calretinin and ultraviolet opsin in order to provide positive cell type identification. Northern and Western blots showed double expression levels per microgram of RNA and protein, respectively, in the rd/rd retina compared with wild-type. However, the total amount of Gpi1 protein per retina was indistinguishable. Gpi1 immunoreactivity was found in ganglion, amacrine, horizontal and bipolar cells, but not in rods, cones, pigment epithelium and Muller cells. This distribution explains why the absolute amounts of Gpi1 protein were not appreciably different between wild-type and the rd/rd phenotype, where rods and cones are absent, whilst the relative contribution of Gpi1 to the total protein and RNA pools differed. Some extracellular immunoreactivity was observed in the photoreceptor matrix around cones in freshly fixed tissue only, which could possibly reflect a role as a cytokine. We propose that glycolysis in Gpi1-negative cells proceeds entirely through the pentose phosphate pathway, creating NADPH at the cost of organic carbon. We hypothesize that the unique metabolic needs of photoreceptors justify this trade-off.

  • Inner retinal photoreceptors (IRPs) in mammals and teleost fish.

    27 November 2018

    Research over the past decade has provided overwhelming evidence that photoreception in the vertebrate eye is not confined to the rods and cones. The discovery of non-rod, non-cone ocular photoreceptors in mammals and fish arose from quite different lines of investigation. In transgenic mice entirely lacking functional rod and cone photoreceptors a range of responses to light, including the regulation of the circadian system and a pupillary light reflex, are preserved. Electrophysiological and imaging approaches were then able to characterise a coupled plexus of directly light sensitive ganglion cells. Most recently action spectroscopy has shown that a novel 'blue-light' sensitive photopigment based upon opsin/vitamin A (OP480) mediates these responses to light. Several candidate genes have emerged for OP480, with melanopsin being by far the strongest. A definitive link, however, between this gene and OP480 has still to be established. In contrast to the mammals, the discovery of inner retinal photoreceptors (IRPs) in fish started with the discovery of a new gene family (VA opsin). The teleost VA opsins form functional photopigments and are expressed in several different types of inner retinal neuron, including retinal horizontal cells. Recent studies have investigated the electrical properties of these photosensitive neurones, but their light-sensing role remains a matter of speculation. Thus the study of IRP is developing along quite separate lines. In the mammals the research is directed towards a molecular identification of the photopigment (OP480) and its cascade, whilst in fish the major effort is directed towards identifying a role for these novel photoreceptors using physiological approaches. The discovery of IRPs in the vertebrates tells us that despite 150 years of research, we still have much to learn about how the eye processes light.

  • Characterization of an ocular photopigment capable of driving pupillary constriction in mice.

    27 November 2018

    This work demonstrates that transgenic mice lacking both rod and cone photoreceptors (rd/rd cl) retain a pupillary light reflex (PLR) that does not rely on local iris photoreceptors. These data, combined with previous reports that rodless and coneless mice show circadian and pineal responses to light, suggest that multiple non-image-forming light responses use non-rod, non-cone ocular photoreceptors in mice. An action spectrum for the PLR in rd/rd cl mice demonstrates that over the range 420-625 nm, this response is driven by a single opsin/vitamin A-based photopigment with peak sensitivity around 479 nm (opsin photopigment/OP479). These data represent the first functional characterization of a non-rod, non-cone photoreceptive system in the mammalian CNS.

  • Vertebrate ancient (VA) opsin and extraretinal photoreception in the Atlantic salmon (Salmo salar).

    27 November 2018

    A member of a new photopigment family first isolated from teleost fish, vertebrate ancient (VA) opsin, has recently been shown to form a functional photopigment and to be expressed within a subset of horizontal and amacrine cells of the inner retina. These sites of expression (and structural features) of VA opsin suggest that this photopigment might mediate non-image-forming light-detection tasks. We attempted to gain support for this hypothesis by examining the expression of VA opsin within the central nervous system (CNS) (pineal and deep brain) of the Atlantic salmon Salmo salar. In addition, we examined the sites of rod-opsin, cone-opsin and &agr; -transducin expression within the salmon CNS to provide a more complete description of the extraretinal photoreceptors of a teleost vertebrate. We show that multiple populations of cells within the salmon CNS appear to contain photoreceptors: VA opsin was strongly expressed in the pineal organ and in bilateral columns of subependymal cells in the epithalamus; anti-cone-opsin antibodies labelled cells within the pineal and numerous cells in the anterior hypothalamus (suprachiasmatic nucleus, nucleus preopticus magnocellularis, nucleus preopticus parvocellularis); anti-rod-opsin antibodies labelled cells within the pineal but no other areas within the central brain; and anti- &agr; -transducin antibodies labelled cells within the pineal and the ventral telencephalon. Collectively, our results suggest that VA opsin is a photopigment specialised for irradiance detection tasks within the eye, pineal and central brain, and that the salmon has multiple and varied populations of photoreceptors within the CNS. We review the significance of these findings within the broad context of vertebrate extraretinal photoreception.

  • NIHR LCRN Studies

    30 June 2016

    The Critical Care Research Group undertakes a number of studies that are adopted by the NIHR local research network portfolio.

  • HAVEN

    10 May 2016

    The HAVEN project is funded by the Health Innovation Challenge Fund, a joint venture supported by the Wellcome Trust and the Department of Health.

  • HAVEN

    10 May 2016

    The HAVEN project is funded by the Health Innovation Challenge Fund, a joint venture supported by the Wellcome Trust and the Department of Health.

  • OXVASC Study

    15 January 2013

  • Preventing a Stroke

    15 January 2013

  • Research results

    15 January 2013

  • Useful Links

    15 January 2013

  • Directions

    15 January 2013

  • Frequently Asked Questions

    15 January 2013

  • ABCD Tool

    15 January 2013

  • Oxford Vascular Study

    26 August 2016

    CPSD

    The Oxford Vascular Study (OxVasc) investigates vascular diseases (e.g. strokes, heart attacks) in patients registered with eight general practices in Oxfordshire. We run a rapid-access clinic for patients with suspected Transient Ischaemic Attacks (TIAs) or minor strokes.

  • OPTIMA

    26 August 2016

    CPSD

    The Oxford Project to Investigate Memory and Ageing (OPTIMA) started in 1988 and the last LEAD participants were seen in March 2015. We are no longer recruiting to any of the cohorts. However, we are currently creating the OPTIMA Legacy Resource from which data collected from the OPTIMA cohorts is available and samples are biobanked and available. Brain tissue is available as part of the Brains For Dementia Research (BDR) collection.

  • Models of Brain Decision Networks

    21 July 2014

    DCN

    Our group uses computer simulations and mathematical analyses to understand the information processing and activity dynamics of brain networks underlying decision making. We use these models to investigate how neural circuits work in the healthy state, how their dynamics deteriorate in neurological disorders, and how their dynamics and information processing may be best restored by treatments.

  • Anaesthesia Neuroimaging Research Group

    26 November 2018

    NDA

    Our group uses multimodal neuroimaging to understand the changes in the brain under anaesthesia and during altered states of consciousness.

  • Translational Molecular Neuroscience Group

    14 February 2018

    NDCN

    Drug discovery in neuroscience is very challenging but the need is greater than ever. Perhaps the most important factor for successfully developing an effective therapy, is the identification of human disease relevant drug targets. Our group aims to elucidate the pathophysiological basis of human neurological disorders from genetic molecular networks to complex neural systems using human genetics, human models and human tissue wherever possible.

  • Congenital Myasthenia Service

    15 January 2013

    DCN

    We provide a nationally commissioned specialised service for the diagnosis and management of children and adults in whom a congenital myasthenic syndrome is suspected.

  • Breathe Oxford

    13 May 2014

    NDA

  • Cognitive and Motivational Disorders

    6 July 2018

    DCN NDCN

    Our group studies changes in motivation, memory and decision-making that occur in neurological disease. We combine behavioural, neuroimaging, and pharmacological experiments to apply cognitive neuroscience to clinical problems.

  • Oxford University Global Surgery Group

    1 August 2018

    The Oxford University Global Surgery Group brings together Medical Sciences Division clinicians in surgery, anaesthesia, obstetrics and gynaecology with an interest in global surgical issues.

  • Oxford Epilepsy Research Group

    2 April 2014

    DCN

    We are a forward-looking dynamic group interested in all aspects of clinical and experimental epileptology with an emphasis on clinically relevant research. The Group draws together all relevant disciplines across Oxford University Hospitals and the University of Oxford.