Sensing the Light, but Not to See: Primitive Organism’s Photosensitive Cells May Be Ancestral to ‘Circadian Receptors’ in Mammalian Retina

Feb. 6, 2013 — Among the animals that are appealing “cover models” for scientific journals, lancelets don’t spring readily to mind. Slender, limbless, primitive blobs that look pretty much the same end to end, lancelets “are extremely boring. I wouldn’t recommend them for a home aquarium,” says Enrico Nasi, adjunct senior scientist in the MBL’s Cellular Dynamics Program. Yet Nasi and his collaborators managed to land a lancelet on the cover of The Journal of Neuroscience last December. These simple chordates, they discovered, offer insight into our own biological clocks.

The head of the marine invertebrate amphioxus (Branchiostoma floridae), magnified 15 times. Amphioxus are the most ancient of the chordates (animals whose features include a nerve cord), according to molecular analysis. They are important to the study of the origin of vertebrates. (Credit: Photo by Maria del Pilar Gomez)


Nasi and his wife, MBL adjunct scientist Maria del Pilar Gomez, are interested in photo-transduction, the conversion of light by light-sensitive cells into electrical signals that are sent to the brain. The lancelet, also called amphioxus, doesn’t have eyes or a true brain. But what it does have in surprising abundance is melanopsin, a photopigment that is also produced by the third class of light-sensitive cells in the mammalian retina, besides the rods and cones. This third class of cells, called “intrinsically photosensitive retinal ganglion cells” (ipRGCs), were discovered in 2002 by Brown University’s David Berson and colleagues. Now sometimes called “circadian receptors,” they are involved in non-visual, light-dependent functions, such as adjustment of the animal’s circadian rhythms.

“It seemed like colossal overkill that amphioxus have melanopsin-producing cells,” Nasi says. “These animals do nothing. If you switch on a light, they dance and float to the top of the tank, and then they drop back down to the bottom. That’s it for the day.” But that mystery aside, Gomez and Nasi realized that studying amphioxus could help reveal the evolutionary history of the circadian receptors.

As so it has. In 2009, Gomez and Nasi isolated the animal’s melanopsin-producing cells and described how they transduce light. In their recent paper, they tackled the puzzling question of why the light response of these amphioxus cells is several orders of magnitude higher than that of their more sophisticated, presumed descendents, the ipRGCs. (In mammals, the ipRGCs relay information on light and dark to the biological clock in the hypothalamus, where it is crucial for the regulation of circadian rhythms and associated control of hormonal secretion.)

By detailing how the large light response occurs in the amphioxus cells, Gomez and Nasi could relate their observations to the functional changes that may have occurred as the circadian receptors evolved and “eventually tailored their performance to the requirements of a reporter of day and night, rather than to a light sensor meant to mediate spatial vision.” The light-sensing cells of amphioxus, they discovered, may be the “missing link” between the visual cells of invertebrates and the circadian receptors in our own eyes.

Story Source:

The above story is reprinted from materials provided byMarine Biological Laboratory. The original article was written by Diana Kenney.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal References:

  1. C. Ferrer, G. Malagon, M. d. P. Gomez, E. Nasi.Dissecting the Determinants of Light Sensitivity in Amphioxus Microvillar Photoreceptors: Possible Evolutionary Implications for Melanopsin Signaling.Journal of Neuroscience, 2012; 32 (50): 17977 DOI:10.1523/JNEUROSCI.3069-12.2012
  2. M. del Pilar Gomez, J. M. Angueyra, E. Nasi. Light-transduction in melanopsin-expressing photoreceptors of AmphioxusProceedings of the National Academy of Sciences, 2009; 106 (22): 9081 DOI:10.1073/pnas.0900708106
Marine Biological Laboratory (2013, February 6). Sensing the light, but not to see: Primitive organism’s photosensitive cells may be ancestral to ‘circadian receptors’ in mammalian retina. ScienceDaily. Retrieved February 7, 2013, from

Brain Research Provides Clues to What Makes People Think and Behave Differently

Feb. 6, 2013 — Differences in the physical connections of the brain are at the root of what make people think and behave differently from one another. Researchers reporting in the February 6 issue of the Cell Press journal Neuron shed new light on the details of this phenomenon, mapping the exact brain regions where individual differences occur. Their findings reveal that individuals’ brain connectivity varies more in areas that relate to integrating information than in areas for initial perception of the world.

Intersubject variability was quantified at each surface vertex across 23 subjects after correction for underlying intrasubject variability. Values below the global mean are shown in cool colors while values above the global mean are shown in warm colors. (Credit: Neuron, Mueller et al.)

“Understanding the normal range of individual variability in the human brain will help us identify and potentially treat regions likely to form abnormal circuitry, as manifested in neuropsychiatric disorders,” says senior author Dr. Hesheng Liu, of the Massachusetts General Hospital.

Dr. Liu and his colleagues used an imaging technique called resting-state functional magnetic resonance imaging to examine person-to-person variability of brain connectivity in 23 healthy individuals five times over the course of six months.

The researchers discovered that the brain regions devoted to control and attention displayed a greater difference in connectivity across individuals than the regions dedicated to our senses like touch and sight. When they looked at other published studies, the investigators found that brain regions previously shown to relate to individual differences in cognition and behavior overlap with the regions identified in this study to have high variability among individuals. The researchers were therefore able to pinpoint the areas of the brain where variable connectivity causes people to think and behave differently from one another.

Higher rates of variability across individuals were also displayed in regions of the brain that have undergone greater expansion during evolution. “Our findings have potential implications for understanding brain evolution and development,” says Dr. Liu. “This study provides a possible linkage between the diversity of human abilities and evolutionary expansion of specific brain regions,” he adds.

Story Source:

The above story is reprinted from materials provided byCell Press, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

  1. Sophia Mueller, Danhong Wang, Michael D. Fox, B.T. Thomas Yeo, Jorge Sepulcre, Mert R. Sabuncu, Rebecca Shafee, Jie Lu, Hesheng Liu. Individual Variability in Functional Connectivity Architecture of the Human BrainNeuron, 2013; 77 (3): 586 DOI:10.1016/j.neuron.2012.12.028
Cell Press (2013, February 6). Brain research provides clues to what makes people think and behave differently. ScienceDaily. Retrieved February 7, 2013, from

Possible Cause Of, and Treatment For, Non-Familial Parkinson’s

Feb. 6, 2013 — Columbia University Medical Center (CUMC) researchers have identified a protein trafficking defect within brain cells that may underlie common non-familial forms of Parkinson’s disease. The defect is at a point of convergence for the action of at least three different genes that had been implicated in prior studies of Parkinson’s disease. Whereas most molecular studies focus on mutations associated with rare familial forms of the disease, these findings relate directly to the common non-familial form of Parkinson’s.


The study was published today in the online edition of the journalNeuron.

The defective pathway is called the “retromer” pathway, in part because it can guide the reutilization of key molecules by moving them back from the cell surface to internal stores. In this study, defects in the retromer pathway also appear to have profound effects on the cell’s disposal machinery, which may explain why Parkinson’s disease brain cells ultimately accumulate large protein aggregates. The trafficking defects associated with Parkinson’s can be reversed by increasing retromer pathway activity, suggesting a possible therapeutic strategy. No current therapies for Parkinson’s alter the progression of the disease.

The researchers also found evidence that, even in unaffected individuals who simply carry common genetic variants associated with an increased risk of Parkinson’s disease, these molecular changes are at work. This supports the notion that early treatment approaches will be important in tackling Parkinson’s disease.

“Taken together, the findings suggest that drugs that target the retromer pathway could help prevent or treat Parkinson’s,” said study leader Asa Abeliovich, MD, PhD, associate professor of pathology and cell biology and of neurology in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at CUMC.

In recent years, through genome-wide association studies (GWAS), researchers have identified about 10 common genetic variants that appear to have small effects on the risk of non-familial Parkinson’s, However, it has been hard to delve deeper into the impact of these variants. “When you look at patient brain tissue at autopsy, it’s usually too late — all the critical dopamine neurons are long gone and the damage has been done,” said Dr. Abeliovich.

In the current study, Dr. Abeliovich and his CUMC colleagues used an unusually broad array of approaches — including analyses of Parkinson’s disease-associated genetic variations, patient brain tissue, in vitro tissue culture studies of brain neurons, and fruit fly (Drosophila) models that harbor genetic variants related to those associated with Parkinson’s disease.

The researchers found that common variants in two genes previously linked to Parkinson’s disease, LRRK2 and RAB7L1, led to an unexpectedly similar impact on human brain tissue. The effects of the variants were found to be highly overlapping, pointing to a common pathway of action. Prominent cellular changes were observed in the retromer pathway, which is involved in the trafficking of proteins from the Golgi apparatus (which packages proteins for delivery to other cell components) to the lysosomes (which recycle proteins and other molecules). Mutations that affect the retromer pathway have also been found in familial Parkinson’s disease. Earlier studies from Columbia’s Taub Institute have shown that genetic variants in genes associated with retromer function are linked to Alzheimer’s disease and retromer component levels appear altered in Alzheimer’s disease brains, suggesting a broader role for retromer dysfunction in neurodegenerative diseases of aging, according to Dr. Abeliovich.

The impact of the RAB7L1 and LRRK2 variants was apparent even in individuals with no signs or symptoms of Parkinson’s disease. This suggests that there is a pre-disease state in unaffected carriers of the two genetic variants that favors early disease onset and that, in theory, could be targeted therapeutically.

The CUMC researchers also demonstrated that overexpression of one of the variants, RAB7L1, can overcome the effects of the other variant. Similarly, expression of VPS35, a gene involved in the retromer pathway, can suppress LRRK2 mutant pathology. “It will be interesting to look for drugs that directly target these retromer components or that more generally promote flow through the pathway,” said Dr. Abeliovich.

The title of the paper is “RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson’s disease risk.” The other contributors are David A. Macleod, Herve Rhinn, Tomoki Kuwahara, Ari Zolin, Gilbert Di Paolo, Brian D. McCabe, Lorraine N. Clark, and Scott A. Small, all at CUMC.

The study was supported by grants from the Michael J. Fox Foundation and the National Institutes of Health (NS064433, NS060876, NS060113, A6008702, AG025161, and AG08702-21.


Story Source:

The above story is reprinted from materials provided byColumbia University Medical Center.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

  1. David A. MacLeod, Herve Rhinn, Tomoki Kuwahara, Ari Zolin, Gilbert Di Paolo, Brian D. MacCabe, Karen S. Marder, Lawrence S. Honig, Lorraine N. Clark, Scott A. Small, Asa Abeliovich. RAB7L1 Interacts with LRRK2 to Modify Intraneuronal Protein Sorting and Parkinson’s Disease RiskNeuron, 2013; 77 (3): 425 DOI:10.1016/j.neuron.2012.11.033
Columbia University Medical Center (2013, February 6). Possible cause of, and treatment for, non-familial Parkinson’s. ScienceDaily. Retrieved February 7, 2013, from

Environmental Factors Determine Whether Immigrants Are Accepted by Cooperatively Breeding Animals

Feb. 6, 2013 — Cichlid fish are more likely to accept immigrants into their group when they are under threat from predators and need reinforcements, new research shows. The researcher suggests that there are parallels between cooperatively breeding fish’s and humans’ regulation of immigrants. The research was published February 6, 2013, in the journalProceedings of the Royal Society B.

The Princess of Lake Tanganyika (Neolamprologus pulcher), a cichlid fish which is popular in home aquariums, are cooperatively breeding fish with a dominant breeding pair and several ‘helper’ fish that do not normally breed but instead assist with raising offspring. Helpers also play a crucial role in defending the group’s territory against outsiders — although helpers also compete with the breeders for resources and reproductive opportunities.

The researchers, led by Dr Markus Zӧttl of the University of Cambridge, wanted to find out how environmental pressures might influence the acceptance of new immigrants. Zӧttl, who conducted the research while at the University of Bern, said: “All animal societies are affected in one or another by immigration and when we seek to understand social organisation we need to understand which environmental factors influence processes like immigration.”

A subdivided tank was used to carry out a series of tests in which different scenarios were observed. For the study, a breeding pair (which would be responsible for deciding whether a newcomer would be allowed to join the group) was placed in one compartment next to a compartment containing either a fish predator, an egg predator, a herbivore fish or no fish at all. An immigrant was placed in a third, adjoining compartment. The breeding pair was then exposed to the different fish in compartment two. The researchers then observed whether the type of fish they were exposed to would affect whether they accepted the immigrant fish from the third compartment.

The researchers found that breeders are less aggressive to immigrants and more likely to accept the unknown and unrelated fish as a member of their group when they are simultaneously exposed to predators. They concluded that cichlid fish are more likely to accept immigrants into their group when they are under threat from predators and can be used to increase their defences.

Dr Zӧttl added: “Our fish resemble human societies’ view of immigration in two crucial aspects: The need for help in the territory takes precedence, and it seems to be a strategy of the territory holders to accept immigrants only when they need assistance with territory defence. This resembles human societies which organise immigration according to the demand in the society by encouraging skilled immigration when certain types of labour are in short supply.”

The researchers also found that the fish appear to consider future threats. When egg predators were presented to a breeding pair who had not yet spawned they accepted new incomers. Their acceptance of reinforcements in the form of immigrant fish suggests that that the egg predator was viewed as a threat.

Dr Zӧttl concluded: “This behaviour suggests that breeders of this species might be able to anticipate a potential threat — and it seems to resemble the future planning evident in birds and apes.”

Story Source:

The above story is reprinted from materials provided byUniversity of Cambridge. The original story is licensed under a Creative Commons license.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

University of Cambridge (2013, February 6). Environmental factors determine whether immigrants are accepted by cooperatively breeding animals. ScienceDaily. Retrieved February 7, 2013, from

Nothing Fishy About Swimming With Same-Sized Mates

Feb. 6, 2013 — Same-sized fish stick together, using chemical cues to identify each other.

Have you ever wondered why, and how, shoals of fish are composed of fish of the same size? According to new research by Ashley Ward, from the University of Sydney in Australia, and Suzanne Currie, from Mount Allison University in Canada, fish can use a variety of different sensory cues to locate shoal-mates, but they are able to use chemical cues to find other fish of the same size as themselves. Using these cues, they can form a group with strength in numbers. The work is published online in Springer’s journal, Behavioral Ecology and Sociobiology.

Forming groups is beneficial for animals. One important benefit is the reduction of individual risk from predators. Indeed when animals are in groups, predators are confronted by a number of almost identical prey animals, making it more challenging to select a target.

Dr. Ward said, “Fish typically form shoals with fish of the same size. The key question that motivated our study is this: How on earth does a fish know how big it is? For humans this is trivial — we can stand on a flat surface and see whether we’re taller or shorter than someone, or we can look in a mirror. These options don’t exist for fish, so how do they choose to associate with fish of the same size?”

The scientists explored which of their senses fish use both to assess the size of other individuals, and to determine how big they are themselves. They studied two freshwater shoaling fish species: three-spined stickleback and banded killfish. In a series of experiments, they exposed the fish to a variety of chemical cues — either from fish of the same species of varying sizes or a control, so-called ‘blank’ cue. Chemical cues are formed as fish constantly emit molecules into their surroundings.

Ward continued, “We know the sense of smell is well developed in fish and that they are sensitive to tiny differences in the chemical signature given off by others. So could they smell how big they are themselves and use this as a template to assess the size of others? It seems they can.”

Both species of shoaling fish preferred the chemical cues of same-sized fish than those of larger or smaller fish from their own species. This suggests that the fish were able to determine their own size relative to other fish of the same species, primarily through chemical self-referencing.

“Using chemical cues to locate similarly sized fish of the same species in the wild promotes the formation of shoals, which creates confusion for predators as well as more coordinated, and potentially efficient, patterns of behavior for both activity and nutrition,” concluded Ward.


Story Source:

The above story is reprinted from materials provided bySpringer Science+Business Media.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

  1. Ashley J. W. Ward, Suzanne Currie. Shoaling fish can size-assort by chemical cues aloneBehavioral Ecology and Sociobiology, 2013; DOI: 10.1007/s00265-013-1486-9
Springer Science+Business Media (2013, February 6). Nothing fishy about swimming with same-sized mates. ScienceDaily. Retrieved February 7, 2013, from