Focus on mitochondria in schizophrenia research

Despite advances in genomics in recent years, schizophrenia remains one of the most complex challenges of both genetics and neuroscience. The chromosomal abnormality 22q11 deletion syndrome, also known as DiGeorge syndrome, offers a way in, since it is one of the strongest genetic risk factors for schizophrenia. Out of dozens of genes within the 22q11 deletion, several encode proteins found in mitochondria. A team of Emory scientists, led by cell biologist Victor Faundez, recently analyzed Read more

Fetal alcohol cardiac toxicity - in a dish

Alcohol-induced cardiac toxicity is usually studied in animal models; a cell-culture based approach could make it easier to study possible interventions more Read more

Fighting cancer with combinatorial imagination

Arbiser says he arrived at Tris-DBA-palladium by using his chemist’s imagination, in a “your chocolate landed in my peanut butter” kind of Read more

neuroscience

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.

Posted on by Quinn Eastman in Neuro 1 Comment

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.”

 

Posted on by Quinn Eastman in Neuro 2 Comments

Brain enhancement: can and should we do it?

The Emory Center for Ethics and Emory’s Neuroscience Graduate Program recently co-hosted a symposium discussing the ethics of brain-enhancing technologies, both electronic and pharmacological.

Georgia Tech biomedical engineer Steve Potter explained his work harnessing the behavior of neurons grown on a grid of electrodes. The neurons, isolated from rats, produce bursts of electrical signals in various patterns, which can be “tuned” by the inputs they receive.

“The cells want to form circuits and wire themselves up,” he said.

As for future opportunities, he cited the technique of deep brain stimulation as well as clinical trials in progress, including one testing technology developed by the company Neuropace that monitors the brain’s electrical activity for the purpose of suppressing epileptic seizures. Similar technology is being developed to help control prosthetic limbs and could also promote recovery from brain injury or stroke, he said. Eventually, electrical stimulation that is not modulated according to feedback from the brain will be seen as an overly blunt instrument, even “barbaric,” he said.

Mike Kuhar, a neuroscientist at Yerkes National Primate Research Center, introduced the topic of cognitive enhancers or “smart drugs.” He described one particular class of proposed cognitive enhancers, called ampakines, which appear to improve functioning on certain tasks without stimulating signals throughout the brain. Kuhar questioned whether “smart drugs” pose unique challenges, compared to other types of drugs. From a pharmacology perspective, he said there is less distinction between therapy and enhancement, compared to a perspective imposed by regulators or insurance companies. He described three basic concerns: safety (avoiding toxicity or unacceptable side effects), freedom (lack of coercion from governments or employers) and fairness.

“Every drug has side effects,” he said. “There has to be a balance between the benefits versus the risks, and regulation plays an important role in that.”

He identified antidepressants and treatments for attention deficit-hyperactivity disorder or the symptoms of Alzheimer’s disease as already raising similar issues. The FDA has designated mild cognitive impairment associated with aging as an open area for pharmaceutical development, he noted.

James Hughes, a sociologist from Trinity College and executive director of the Institute for Ethics and Emerging Technologies, welcomed new technologies that he said could not only treat disease, but also enhance human capabilities and address social challenges such as criminal rehabilitation. However, he did identify potential “Ulysses problems”, where users of new technologies would need to exercise control and judgment.

In contrast, historian and Judaic scholar Hava Tirosh-Samuelson, from Arizona State University, decried an “overly mechanistic and not culturally-based understanding of what it means to be human.” She described transhumanism as a utopian extension of 19th century utilitarianism as expounded by thinkers such as Jeremy Bentham.

“Is the brain simply a computational machine?” she asked.

The use of military metaphors – such as “the war on cancer” – in the context of mental illness creates the false impression that everything is correctable or even perfectable, she said.

Emory neuroscience program director Yoland Smith said he wants ethics to become a strong component of Emory’s neuroscience program, with similar discussions and debates to come in future years.

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National Academy of Sciences recognizes Yerkes Primate Center neuroscientist

Elizabeth A. Buffalo, PhD

The National Academy of Sciences (NAS) has recognized 13 individuals with awards acknowledging extraordinary scientific achievements in the areas of biology, chemistry, physics, economics and psychology.

Elizabeth A. Buffalo, PhD, a researcher at the Yerkes National Primate Research Center, is one of two recipients of the Troland Research Awards. Buffalo is being honored for innovative, multidisciplinary study of the hippocampus and the neural basis of memory. Troland Research Awards of $50,000 are given annually to recognize unusual achievement by young investigators and to further empirical research in experimental psychology.

The recipients will be honored in a ceremony on Sunday, May 1, during the NAS 148th annual meeting.

Posted on by Holly Korschun in Neuro Leave a comment

Renowned Scientist Recipient of Emory’s First Annual Neuroscience and Ethics Award

Michael Gazzaniga, PhD

Michael Gazzaniga, PhD, will deliver the lecture “Determinism, Consciousness and Free Will.”

Emory University Center for Ethics, Yerkes National Primate Research Center and The Neuroscience Initiative will present the First Annual Neuroscience and Ethics Award Lecture, “Determinism, Consciousness and Free Will” on January 18 at 4 pm at Emory’s Harland Cinema at the Dobbs University Center.

The guest speaker, and first to be recognized with this award, is Michael Gazzaniga, PhD, a scientist and author considered one of the pioneers in the emerging field of cognitive neuroscience.

“Dr. Gazzaniga is a world renowned scientists who, in addition to his other accomplishments, pioneered the study of split-brained patients and so revealed how the different hemispheres of our brains function,” says Paul Root Wolpe, PhD, director of the Emory University Center for Ethics.

“He has won our First Annual Emory Neuroscience and Ethics Award because, throughout his career, he has tried to apply his scientific understandings to improve the human condition, including serving on President Bush’s Bioethics Commission and publications such as his book The Ethical Brain.  I can think of no finer choice to be the first recipient of this Award.”

Gazzaniga founded and presides over the Cognitive Neuroscience Institute and is editor-in-chief emeritus of the Journal of Cognitive Neuroscience, which he also founded.  In addition, he is the one of the co-founders of the Cognitive Neuroscience Society, which was named in the late 1970’s.

In 1997, Gazzaniga was elected to the American Academy of Arts & Sciences.  He is the past-president of the Association for Psychological Science, served on the President’s Council on Bioethics and, in 2005, was elected to the National Academies Institute of Medicine. In 2009, he presented the Gifford Lectures at the University of Edinburgh.

Gazzaniga’s book The Ethical Brain describes in laymen’s language how the brain develops a value system, and the ethical dilemmas facing society as our comprehension of the brain expands.

For more information, contact Jamila Garrett-Bell.

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New drug strategy against fragile X

Even as clinical trials examining potential treatments for fragile X syndrome gain momentum, Emory scientists have identified a new strategy for treating the neurodevelopmental disorder.

In a paper recently published in Journal of Neuroscience, a team led by cell biologist Gary Bassell shows that PI3 kinase inhibitors could restore normal appearance and levels of protein production at the synapses of hippocampal neurons from fragile X model mice. The next steps, studies in animals, are underway.

“This is an important first step toward having a new therapeutic strategy for fragile X syndrome that treats the underlying molecular defect, and it may be more broadly applicable to other forms of autism,” he says.

A recent Nature Biotechnology article describes pharmaceutical approaches to autism and fragile X.

Posted on by Quinn Eastman in Neuro 1 Comment