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keithr1024
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ganglion lump
« on: Oct 22nd, 2006, 9:16am » |
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there was talk of the cluster lump in earlier post and after that i led me to do some searching and i found this under human circadian rhythm Melanopsin is a photopigment found in specialized ganglion cells of the retina that are involved in the regulation of circadian rhythms and pupillary reflex. In structure, melanopsin is an opsin, a variety of G-protein-coupled receptor. It is presumed that melanopsin signals through a G-protein of the Gq family, as invertebrate opsins are known to do, but this is not firmly established. It is also believed to be similar to invertebrate opsins in possessing an intrinsic photoisomerase activity. i really don't know if this has any bearing on ch's but it might lead some of the members to search in a productive direction.
keep on keeping on everyone! did more searching and foind this and i think it's interestimg When light activates the melanopsin signaling system, the melanopsin-containing ganglion cells discharge nerve impulses, which are conducted through their axons in the optic nerve to specific brain targets. These targets include the suprachiasmatic nucleus of the hypothalamus (the master pacemaker of circadian rhythms) and the olivary pretectal nucleus (a center responsible for controlling the pupil of the eye). Melanopsin ganglion cells are thought to influence these targets by releasing from their axon terminals the neurotransmitters glutamate and pituitary adenylate cyclase activating polypeptide (PACAP).
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LeLimey
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Re: ganglion lump
« Reply #1 on: Oct 22nd, 2006, 10:56am » |
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Thanks for that Keith, its very interesting.
Have a look at the articles on Neurogenesis by Peter May in the OUCH US Newsletter, its a series and can be found here at http://www.ouch-us.org/newsletters/newsletters.shtml so read through them as I think that may interest you alot
Helen
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pattik
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Re: ganglion lump
« Reply #2 on: Oct 22nd, 2006, 11:20am » |
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Keith, As Helen said, it's a very interesting and complex bit of studying. I have tried light therapy in the past with uncertain results. It's difficult for an individual to determine if light is being used at the correct times and amounts. The OUCH site has a good page on the hypothalamus:
http://www.ouch-us.org/chgeneral/hypothalamus/hypothalamus1.htm
Dr Goadsby has done some studying of polypeptides in CH'ers, and I have a particular interest in the vasoactive intestinal polypeptide (VIP), since I experience GI symptoms along with CH hits. Here is one of his studies:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed &list_uids=7518321&dopt=Abstract
Good luck with you searches.
patk
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The voyage of discovery is not about seeking new landscapes, it's about having new eyes--Marcel Proust
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ben_uk
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Re: ganglion lump
« Reply #3 on: Oct 22nd, 2006, 4:58pm » |
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The master clock in mammals, the suprachiasmatic nuclei (SCN). recieves its retinel projections from the retinohyophalamic tract (RHT), which is formed from a small number of distinct ganglion cells. These ganglion cells ( around 1 per cent of the total) tend to be distributed evenly over the entire retina and send an unmapped or random projection to the SCN. Glutamate, a common neurotransmitter, carries the light infomation signal to individual SCN neurones. By contrast, the ganglion cells of the visual sytem send a highly mapped projection to the visual centres of the brain, such that a point on the retina maps precisely to a group of cells in the visual cortex. The visual system is thus able to deduce both how much light there is and where it occurs in specific regions of the environment, whereas the SCN receives only information about the general brightness of environmental light. So the mammalian eye has parallel outputs, providing both image and brightness information.
Mammals use their eyes to detect all light; if the eyes are lost, a mammal is both visually and circadian blind. It will be unable to entrain to light and will free-run for the rest of its days. However, if the eyes of birds, reptiles, amphibians and fish are removed they can still maintain an entrained circadian rhythm. They have several light-sensing "extraocular" photoreceptor organs other than the eyes.
Mammals lost these extraocular photoreceptors during thier unique evolutionary history. All modern mammals are derived from nocturnal, burrowing insectivorous or omnivorous animals that were living about 100 million years ago. Primitive mammals would have spnt their days in burrowsand then emerged at dusk (Young, 1962). Extraocular photoreceptors, are located under the skull, may not have been sufficiently sensitive to discriminate twilight changes.
Despite the fact that eye loss results in free-running rhythms in mammals, claims have been made from time to time that they have non-ocular photoreceptors.There was even a recent suggestion that humans had photoreceptors behind the knee, as bright light shone there apparently shifted human circadian rhythms. It was a charming thought but unfortunately nobody could replicate the findings. All the experimental evdence points to light entrainment of the circadian system of mammals occurring exclusively via photoreceptors within the eye. Eye loss in every mammal ever studied, including humans, results in free running circadian rhythm.
The sensory task of generating an image for the visual system is very different from the sensory task of collecting light for the regulation and entrainment of the clock. The previously reasonable assumption that retinal rods and cones detect light for both these forms of light sensing was a gross oversimplification. Although the entraining photoreceptors of mammals are clearly located in the eye,niether the rods nor the cones are required for this task, and there exists another photoreceptor within the eye.
The identification of the non-rod, non-cone, photoreceptor resulted from a series of experiments over 10 years in Russell Foster's laboratory. The group started out by looking at mice with naturally occurring genetic disorders of the rods and cones of the eye. The experimental plan was to correlate rod and cone photoreceptor loss with a loss in sensitivity of the circadian system to light. The first mutant mice studied lacked all rods and most of the cones. This mutant strain of mice, known as the retinal degeneration or rd/rd mouse,is visually blind. But but despite the massive (though not complete) loss of their rods and cones, these animals had apparently normal circadian responses to light.
These surprising and unexpected findings were met with either polite lack of interest or hostile rejection. The eye has been the subject of serious study for some 200 years, and in broad terms its function was thought to be understood. The conventional understanding was light-sensitive rods and cones of the outer retina transduce light, and the cells of the inner retina provide the initial stages of signal processing before topographically mapped signals travel down the optic nerve to specific sites in the brain for advanced visual processing. Even though there was clear evidence of different visual and circadian pathways from the retina, including the side-shoot that linked into the SCN, there was a strong belief among many biologists that there was a single photoreception apparatus. It seemed inconeivable that something as important as an unrecognised ocular photoreceptor could have been missed. The feeling was that there was no need to upset the neat story of vision, and its evolutionary origins, with new photoreceptors.
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ben_uk
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Re: ganglion lump
« Reply #4 on: Oct 22nd, 2006, 5:01pm » |
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This conventional wisdom was challenged by a few researchers interested in how vertebrate clocks are regulated by light and whose background and training were rooted not in vision reseach but in fields such as circadian and repoductive physiology and animal behaviour. These researchers were not trained as visual scientists, but their naivete was combined with an acute awareness that the vertebrate central nervous system is packed with "enigmatic" photoreceptors that help adjust circadian rhythms to the local light environment. They were aware that birds, reptiles, amphibians and fish employ specialised photosensory cells in the basal brain and pineal to regulate their circadian rhythms. Foster's own undergraduate tutor was Alan Roberts, who introduced him to the study of pineal photoreception in frogs. This theme was developed in doctoral studies with Sir Brian Follett on the interplay of light and seasonal reproduction in birds. Michael Menaker, who at the time was on a sabbatical year at Bristol University, took an interest in this work and suggested that it could be developed using mice with hereditary retinal disorders.
Circadian Biologists had no problems with organisms having a whole array of photoreceptors performing visual and/or circadian functions. This made it much easier for them to accept the notion of dedicated photoreceptors in the retina separated from the visual system.It seemed perfectly resonable to ask whether rods, cones, uncharacterised retinal photoreceptors or a combination thereof might regulate the circadian rhythms of mammals, and these questions have radically altered the way in which we think about the eye as a sensory organ.
But when you are out to convince the sceptics, or trespass across the disiplinary fields erected by scientists, then the science has to be like Caesar's wife - beyond reproach. Further studies, using different mouse mutants in different laboratories around the world, were able to repeat the Foster laboratory's observations and showed that the loss of visual responses due to retinal disease did not block circadian responses to light. At the very least, these studies in mice, and other rodents such as the "blind mole rat" (David-Grey et al.,199 , showed that the processing of light by the eye for vision was very different from the way in which the eye processed information for the clock. Rodents could be visually blind but not circadian blind. However, suggestive as these early studies were, they did not conclusively demontrate the existence of a new ocular photoreceptor. Although the rods and cones were massively reduced in these rodents, they were never completly eliminated. There was the possibility that even a small number of rods and cones might still be sufficient to maintain normal circadian responses to light.
Rather than wait for the chance discovery of a mutant mammal with absolutely no rods and cones, a new mouse strain was developed, known affectionately if unoriginally as the rd/rd cl mouse. This mouse had no rods whatsoever. Although completely visually blind, such mice still showed the normal circadian responses to light in the laboratory. By blocking the light reaching the eye, the effects of light on the cicadian system were abolished, so there had to be a novel photoreceptor. Because these mice lacked an outer retina, the new photoreceptor cells were probably located within the inner retina. The key questions were the nature and location of this photoreceptor, but there were no obvious candidates visible under the microscope.
Science rarely proceeds along straight lines. Chance and serendipity are the researcher's bedfellows. A clue to the mammalian photoreceptor came from work on fish. Quite by accident, Bobby Soni, who was working his doctoral thesis, discovered a new gene in the salmon eye that was similar to the genes that code for rod and cone photopigments, but nevertheless had clear differences.
When photons enter a rod or cone, many of them interact with photopigments. The photopigments of all animals consist of a form of opsin protein that binds a specific type of vitamin A (11-cis-retinaldehyde) to form a photosensitive complex. The absorption of a photon of light by 11-cis-retinaldehyde converts it to an all-trans form. This change in shape of vitamin A alters the opsin, which in turn triggers the phototransduction cascade. This ultimately causes a change in the electrical activity of the photoreceptor cell that is transmitted by neural pathway and ends with what we know as vision.
Soni's key finding was that the new (VA-opsin) gene was not expressed in the salmon's rods and cones. It was found only in certain cells in the inner part of the retina which had not been thought to contain any photoreceptors. This was the first dicovery of a photopigment in the eye that was separate from the rods and the cones (Soni et al 199. Although Soni had been working with fish, the discovery of the new opsin suggested a possible mechanism for non-rod, non-cone photoreception in vertebrates in general.
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ben_uk
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Re: ganglion lump
« Reply #5 on: Oct 22nd, 2006, 5:02pm » |
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Rods and cones are easy to identify microscopically. Although countless microscopic investigations had revealed a huge range of cell types within the inner retina, no one had seen anything that could be conciderd a photoreceptor. Soni's work suggested that if the mammalian equivalent of the salmon VA-opsin could be found and localised, there was a strong presumption that this would be the inner retinal photoreceptor.
A new opsin was soon found . Melanopsin was discovered by Ignacio Provencio in a range of mammals and localised to the ganglion cells that that form the RHT and project to the SCN (Provencio et al., 2000; Hattar et al., 2003) . Furthermore, in vitro, these cells were directly sensitive to light (Berson et al ., 2002; Sekaran et al ., 2003). It looks as though these cells were the non-rod , non-cone photoreceptors. Unfortunately, There is so little melanopsin in the mammalian eye that it has not been possible to produce enough of the protein to do the biochemistry to prove that melanopsin is the photopigment.
An experimental conundrum soon emerged. When the melanopsin gene in a normal mouse was experimentally "turned off", the melanopsin ganglion cells of the RHT were no longer directly light sensitive, and the circadian response to light was diminished, but critically it was far from abolished. Further, when the melanopsin photosensitive ganglion cells in the rodless-and-coneless mice are "turned off", all circadian responses to light completely disappear (Hattar et al 2003). What has to be explained is how it is that rodless-and-coneless mice nevertheless have an apparently normal circadian entrainment to light and melanopsin-deficient normal mice have an attenuated circadian entrainment to light, but melanopsin-deficient rodless-and-coneless mice have no circadian entrainment to light. Somehow the rods and cones must play a part, but rods and cones are not necessary for apparently normal circadian responses to bright light.
Although in the bright light of artificial laboratory conditions the rods and cones are not necessary for the regulation of the circadian system, this does not mean that these photoreceptors play no role in the wild. This could be the answer to the conundrum. Under certain exprimental conditions involving dim light/dark cycles that in some ways more closely resemble the light levels encountered in nature, rodless-and-coneless mice entrain but not with the same precision as normal sighted mice. In addition, electrical recordings made from the SCN of rats by Hilmar Meissl and his colleagues in Frankfurt have demostrated that the rods and cones do send light information to the SCN (Aggelopoulos & Meissl, 2000). It could be that under bright light the contribution of the rods and cones is "swamped" and only becomes apparent in the dimmer light of early dawn and late dusk.
Organisms have to be able to extract time-of-day information from dawn and dusk. Dawn and dusk are not single points but transient events, and during them the amount of light, the spectral composition of the light and the source of light (the position of the sun) all change in a sytematic way. In theory, all these factors could be used and intergrated by the circadian system to detect the phase of the solar cycle. It is possible that the changing colour of the sky at dawn and dusk, and the position of the sun with respect to the horizon, might indeed act as a cue for entrainment in some species.
Different photoreceptors, sampling slightly different aspects of the twilight scene, may allow a more accurate measure of the phase. They also allow an organism to compensate for sudden, acute changes in light environment when say , a cloud passes over the sun, or an animal moves into the shade. Animals in the wild have to cope with both the reliably predictable daily changes and the unpredictable, moment-to-moment fluctuations.
Establishing that ther are photoreceptors other than the classic rods and cones has practical applications. The studies in retinally degenerate mice encouraged studies of circadian functions in blind people. Josephine Arendt and her group at the University of Surry and Charles Czeisler's group at Harvard both identified blind individuals who had eyes but lacked conscious light perception (Czeisler et al. 1995; Lockley et al.,1997). Despite this, some of these individuals were able still to regulate their circadian responses to light. One practical result is that every attempt is now made to preserve an intact eye in people suffering from certain forms of eye disease so that it can perform its circadian function.
From RHYTHMS OF LIFE.
The Biological Clocks that Control the Daily Lives of Every Living Thing
Russell Foster & Leon Kreitzman. ISBN 1 86197 235 0.
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chopmyheadoff
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Re: ganglion lump
« Reply #6 on: Oct 23rd, 2006, 4:29am » |
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<<waits for head to stop spinning . . .
wow
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JeffB
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Re: ganglion lump
« Reply #7 on: Oct 23rd, 2006, 11:21am » |
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Just what I thought!
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LeeS
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Re: ganglion lump
« Reply #8 on: Oct 23rd, 2006, 2:00pm » |
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One of the best books I've read in relation to CH; and CH isn't even mentioned!
-Lee
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George_J
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Re: ganglion lump
« Reply #9 on: Oct 23rd, 2006, 2:04pm » |
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Interesting stuff.
Learning as much as possible about the neural pathways involved in regulating circadian rhythm is certainly of interest--many of us here have a definite seasonal and circadian pattern with CH (including me). It's interesting that there appears to be a second neural pathway from non-rod, non-cone cells in the eye that is implicated in regulation of the biological clock. In actuality, something that might almost be considered a second "sense of sight".
Not too surprising, though, really. There is a separate pathway involved in scent, as well, via Jacobsen's Organ in the nose. Some say it is inactive in human beings, others say it is still active. It's very active in some species of animals, and is used to detect "pheremones".
I don't see what this has to do with a ganglion lump, though. Perhaps I'm missing something.
Best wishes,
George
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It all comes to light in the sheer
Debonair.
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BB
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Re: ganglion lump
« Reply #10 on: Oct 23rd, 2006, 3:31pm » |
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Ganglion simply means a bundle of ( nerve ) cells so you have many ganglions in different parts of the body.
This is different from the cluster ganglion lump I talk about in the other thread, which is the ganglion of the parasympathetic nerve chains, regulating the autonomic nervous system.
These ganglions are in the retina at the back of the eyes and relate to light sensory pathways, affecting the circadian rhythm.
Annette
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chopmyheadoff
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Re: ganglion lump
« Reply #11 on: Oct 24th, 2006, 3:04am » |
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i thought i had found a big ganglion lump on my neck to i went to the doctors -
turns out it was my head !! 
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Barry_T_Coles
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Re: ganglion lump
« Reply #12 on: Oct 24th, 2006, 3:14am » |
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on Oct 24th, 2006, 3:04am, chopmyheadoff wrote:i thought i had found a big ganglion lump on my neck to i went to the doctors -
turns out it was my head !!
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Good thing you didn't think it was a pimple and try to squeeze it. 
Cheers
Barry
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BB
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Re: ganglion lump
« Reply #13 on: Oct 24th, 2006, 3:37am » |
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on Oct 24th, 2006, 3:04am, chopmyheadoff wrote:i thought i had found a big ganglion lump on my neck to i went to the doctors -
turns out it was my head !!
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You need to chop your head off then !
Annette
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chopmyheadoff
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Re: ganglion lump
« Reply #14 on: Oct 24th, 2006, 3:48am » |
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PMSL - iv started something here now havent i LOL
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BB
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Re: ganglion lump
« Reply #15 on: Oct 24th, 2006, 3:59am » |
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Chop, its only a ganglion, deal with it ! Smooch ... 
Annette
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lskilly
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Re: ganglion lump
« Reply #16 on: Oct 24th, 2006, 5:44pm » |
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This makes me wonder if having a retina detatch and being partially blind until the blood cleared in my eye didnt have something to do with me being cluster free for eight years. I can see well of this eye now. And the clusters are back. Right eye same side as my CH. ????
Skilly
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