‘Genetic doppelgangers:’ Emory research provides insight into two neurological puzzles

An international team led by Emory scientists has gained insight into the pathological mechanisms behind two devastating neurodegenerative diseases. The scientists compared the most common inherited form of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) with a rarer disease called spinocerebellar ataxia type 36 (SCA 36). Both of the diseases are caused by abnormally expanded and strikingly similar DNA repeats. However, ALS progresses quickly, typically killing patients within a year or two, while the disease Read more

Emory launches study on COVID-19 immune responses

Emory University researchers are taking part in a multi-site study across the United States to track the immune responses of people hospitalized with COVID-19 that will help inform how the disease progresses and potentially identify new ways to treat it.  The study is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The study – called Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) – launched Friday. Read more

Marcus Lab researchers make key cancer discovery

A new discovery by Emory researchers in certain lung cancer patients could help improve patient outcomes before the cancer metastasizes. The researchers in the renowned Marcus Laboratory identified that highly invasive leader cells have a specific cluster of mutations that are also found in non-small cell lung cancer patients. Leader cells play a dominant role in tumor progression, and the researchers discovered that patients with the mutations experienced poorer survival rates. The findings mark the first Read more

neuroscience

Neurons dominate GDBBS contest-winning images

Lab Land’s editor enjoyed talking with several students about their work at the GDBBS Student Research Symposium last week. Neurons dominate the three contest-winning images. The Integrated Cellular Imaging core facility judged the winners. From left to right:

ContestComposite

1st Place: Stephanie Pollitt, Neuroscience

2nd Place: Amanda York, Biochemistry, Cell and Developmental Biology

3rd Place: Jadiel Wasson, Biochemistry, Cell and Developmental Biology

Larger versions and explanations below.

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Emory labs on LabTV

This summer, video producers from the web site LabTV came to two laboratories at Emory. We are pleased to highlight the first crop of documentary-style videos.

LabTV features hundreds of young researchers from universities and institutes around the United States, who tell the public about themselves and their research. The videos include childhood photos and explanations from the scientists about what they do and what motivates them. Screen Shot 2015-12-18 at 9.14.51 AM

The two Emory labs are: Malu Tansey’s lab in the Department of Physiology, which studies the intersection of neuroscience and immunology, focusing on neurodegenerative disease, and Mike Davis’ lab in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, which is developing regenerative approaches and technologies for heart disease in adults and children. Read more

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Inflammation linked to weakened reward circuits in depression

About one third of people with depression have high levels of inflammation markers in their blood. New research indicates that persistent inflammation affects the brain in ways that are connected with stubborn symptoms of depression, such as anhedonia, the inability to experience pleasure.

The results were published online on Nov. 10 in Molecular Psychiatry.

The findings bolster the case that the high-inflammation form of depression is distinct, and are guiding researchers’ plans to test treatments tailored for it.

Anhedonia is a core symptom of depression that is particularly difficult to treat, says lead author Jennifer Felger, PhD, assistant professor of psychiatry and behavioral sciences at Emory University School of Medicine and Winship Cancer Institute.

“Some patients taking antidepressants continue to suffer from anhedonia,” Felger says. “Our data suggest that by blocking inflammation or its effects on the brain, we may be able to reverse anhedonia and help depressed individuals who fail to respond to antidepressants.”

In a study of 48 patients with depression, high levels of the inflammatory marker CRP (C-reactive protein) were linked with a “failure to communicate”, seen through brain imaging, between regions of the brain important for motivation and reward.

Emory researchers have found that high inflammation in depression is linked to a "failure to communicate" between two parts of the brain: the ventral striatum (VS, vertical cross section) and the ventromedial prefrontal cortex (vmPFC, horizontal).

Emory researchers have found that high inflammation in depression is linked to a “failure to communicate” between two parts of the brain: the ventral striatum (VS, vertical cross section) and the ventromedial prefrontal cortex (vmPFC, horizontal). Images from Felger et al, Molecular Psychiatry (2015).

Neuroscientists can infer that two regions of the brain talk to each other by watching whether they light up in magnetic resonance imaging at the same times or in the same patterns, even when someone is not doing anything in particular. They describe this as “functional connectivity.”

More here.

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Congratulations to AAAS Mass Media fellows

Two Emory graduate students, Anzar Abbas and Katie Strong, will be spending the summer testing their communication skills as part of the AAAS Mass Media fellowship program. The program is supposed to promote science communication by giving young scientists a taste of what life is like at media organizations around the country. Both of Emory’s fellows have already gained some experience in this realm.

Abbas, a Neuroscience student who recently joined brain imaging number cruncher Shella Keilholz‘s lab, will be at Howard Hughes Medical Institute. He is part of the group that recently revived the Science Writers at Emory publication In Scripto.

Strong, a Chemistry student working with Dennis Liotta on selective NMDA receptor drugs, will be at the Sacramento Bee. She has been quite prolific at the American Journal of Bioethics Neuroscience and its Neuroethics Blog.

(Thanks to Ian Campbell, a previous AAAS Mass Media fellow from Emory who worked at the Oregonian, for notifying me on this!)

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Dynamic functional connectivity

How can neuroscientists tell that distant parts of the brain are talking to each other?

They can look for a physical connection, like neurons that carry signals between the two. They could probe the brain with electricity. However, to keep the brain intact and examine cheap oakley function in a living person or animal, a less invasive approach may be in order.

Looking for functional connectivity has grown in popularity in recent years. This is a way of analyzing fMRI (functional magnetic resonance imaging) scans, which measure activity in the brain by looking at changes in blood oxygen. If two regions of the brain “light up” at the same time, and do so in a consistent enough pattern, that indicates that those two regions are connected.*

Functional connectivity networks

Shella Keilholz and her colleagues have been looking at functional connectivity data very closely, and how the apparent connections fluctuate over short time periods. This newer form of analysis is called “dynamic” or “time-varying” functional connectivity. Functional connectivity analyses can be performed while the person or animal in the scanner is at rest, not doing anything complicated.

“Even if you’re lying in the scanner daydreaming, your mind is jumping around,” she says. “But the way neuroscientists usually average fMRI data over several minutes means losing lots of information.”

Keilholz is part of the Wallace H Coulter Department of Biomedical Engineering at Georgia Tech and Emory. She participated in a workshop at the most recent Human Brain Mapping meeting in Seattle devoted to the topic. She says neuroscientists have already started using dynamic functional connectivity to detect differences in the brain’s network properties in schizophrenia. However, some of that information may be noise. Skeptical tests have shown that head motion or breathing can push scientists into inferring connections that aren’t really there. For dynamic analysis especially, preprocessing can lead to apparent correlations between two randomly matched signals.

“I got into this field as a skeptic,” she says. “Several years ago, I didn’t believe functional connectivity really reflects coordinated brain activity.”

Now Keilholz and her colleagues have shown for the first time that dynamic functional connectivity data is “grounded”, because it is linked with changes in electrical signals within the brain. The results were published in July in the journal NeuroImage. The first author is graduate student Garth Thompson. Read more

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Manipulating neurons with light

Welcome to a feature of Lab Land we hope to have on a regular basis! It’s where we explain a word or phrase that is a hot topic of discussion in the science online world and particularly relevant to research going on at Emory.

Optogenetics allows researchers to stimulate specific brain cells with light. It involves introducing light-sensitive proteins from algae into the brain cells of mice, and then using a fiber optic cable to apply a laser signal to the relevant region of the brain.

Optogenetics is a leap beyond previous genetic engineering techniques that made it possible to turn on (or delete) a gene by feeding a mouse some extraneous chemical, such as the antibiotic tetracycline or the anti-hormone tamoxifen. Instead of wondering how long it takes that chemical to make its way into the brain, scientists can literally flick a switch and see near-instantaneous and localized effects. Read more

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Seeing in triangles with grid cells

When processing what the eyes see, the brains of primates don’t use square grids, but instead use triangles, research from Yerkes neuroscientist Beth Buffalo’s lab suggests.

Elizabeth Buffalo, PhD

She and graduate student Nathan Killian recently published (in Nature) their description of grid cells, neurons in the entorhinal cortex that fire when the eyes focus on particular locations.

Their findings broaden our understanding of how visual information makes its way into memory. It also helps us grasp why deterioration of the entorhinal cortex, a region of the brain often affected early by Alzheimer’s disease, produces disorientation.

The Web site RedOrbit has an extended interview with Buffalo. An excerpt:

The amazing thing about grid cells is that the multiple place fields are in precise geometric relation to each other and form a tessellated array of equilateral triangles, a ‘grid’ that tiles the entire environment. A spatial autocorrelation of the grid field map produces a hexagonal structure, with 60º rotational symmetry. In 2008, grid cells were identified Gafas Ray Ban outlet in mice, in bats in 2011, and now our work has shown that grid cells are also present in the primate brain.

Please read the whole thing!

Grid cells fire at different rates depending on where the eyes are focused. Mapping that activity across the visual field produces triangular patterns.

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Fragile X protein: one toggle switch, many circuits

The fragile X protein — missing in the most common inherited form of intellectual disability — plays a central role in neurons and how they respond to external signals. Cell biologist Gary Bassell and his colleagues have been examining how the fragile X protein (FMRP) acts as a “toggle switch.”

Gary Bassell, PhD

FMRP controls the activity of several genes by holding on to the RNAs those genes encode. When neurons get an electrochemical signal from the outside, FMRP releases the RNAs, allowing the RNAs to be made into protein, and facilitating changes in the neurons linked to learning and memory.

The Bassell lab’s new paper in Journal of Neuroscience reveals the role of another player in this process. The first author is postdoctoral fellow Vijay Nalavadi.

The researchers show that neurons modify FMRP with ubiquitin, the cellular equivalent of a tag for trash pickup, after receiving an external signal. In general, cells attach ubiquitin to proteins so that the proteins get eaten up by the proteasome, the cellular trash disposal bin. Here, neurons are temporarily getting rid of FMRP, prolonging the effects of the external signal.

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Default daydreaming linked to Alzheimer’s amyloid

Cut the daydreaming, and you can lessen the neurodegenerative burden on your brain? Surprising new research suggests that how we use our brains may influence which parts of the brain are most vulnerable to amyloid-beta (Aβ), which forms plaques in the brain in Alzheimer’s disease.

Lary Walker, PhD, has been investigating why amyloid accumulation seems to lead to Alzheimer's in humans but not non-human primates

In the June issue of Nature Neuroscience, Yerkes National Primate Research Center scientist Lary Walker and Mathias Jucker from the Hertie Institute for Clinical Brain Research in Tübingen, Germany summarize intriguing recent research on regional brain activity and Aβ accumulation.

Neuroscientists have described a set of interconnected brain regions called the “default mode network,” which appear to be activated during activities such as introspection, memory retrieval, daydreaming and imagination. When a person engages in an externally directed task, such as reading, playing a musical instrument, or solving puzzles, activity in the default network decreases.

The Nature Neuroscience paper, from David Holtzman and colleagues at Washington University St. Louis, suggests prolonged metabolic activation of the default-mode network in mice can render that system vulnerable to Aβ by accelerating Aβ deposition and plaque growth.

This line of research turns the “use it or lose it” idea upside-down. Use the default network too much, and the effect may be harmful. Walker and Jucker suggest why education, for example, appears to head off Alzheimer’s in epidemiological studies: by getting the brain involved in non-default/externally directed mode activity.

This idea has additional consequences that can be tested in the clinic. For example, by increasing metabolism in default-mode regions of the brain, prolonged wakefulness caused by sleep disorders might increase Aβ burden.

Walker and Jucker conclude: “Meanwhile, perhaps the best strategy for lessening soluble Aβ in the default mode network may be simply to work diligently, play hard and sleep well.”

 

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