Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lights, Chemistry, Action: New Method for Mapping Brain Activity

12.04.2013
PET scans monitor brain circuits activated by light, opening new window to brain diseases

Building on their history of innovative brain-imaging techniques, scientists at the U.S. Department of Energy's Brookhaven National Laboratory and collaborators have developed a new way to use light and chemistry to map brain activity in fully-awake, moving animals.

The technique employs light-activated proteins to stimulate particular brain cells and positron emission tomography (PET) scans to trace the effects of that site-specific stimulation throughout the entire brain. As described in a paper published online today in the Journal of Neuroscience, the method will allow researchers to map exactly which downstream neurological pathways are activated or deactivated by stimulation of targeted brain regions, and how that brain activity correlates with particular behaviors and/or disease conditions.

"This technique gives us a new way to look at the function of specific brain cells and map which brain circuits are active in a wide range of neuropsychiatric diseases - from depression to Parkinson's disease, neurodegenerative disorders, and drug addiction - and also to monitor the effects of various treatments," said the paper's lead author, Panayotis (Peter) Thanos, a neuroscientist and director of the Behavioral Neuropharmacology and Neuroimaging Section - part of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Laboratory of Neuroimaging at Brookhaven Lab - and a professor at Stony Brook University. "Because the animals are awake and able to move during stimulation, we can also directly study how their behavior correlates with brain activity," he said.

The new brain-mapping method combines very recent advances in a field known as "optogenetics" - the use of optics (light activation) and genetics (genetically coded light-sensitive proteins) to control the activity of individual neurons, or nerve cells - and Brookhaven's historical development of radioactively labeled chemical tracers to track biological activity with PET scanners.

The scientists used a modified virus to deliver a light-sensitive protein to particular brain cells in rats. Genetic coding can deliver the protein to specifically targeted brain-cell receptors. Then, after stimulating those proteins with light shone through an optical fiber inserted through a tiny tube called a cannula, they monitored overall brain activity using a radiotracer known as ^18FDG, which serves as a stand-in for glucose, the body's (and brain's) main source of energy.

The unique chemistry of ^18FDG causes it to be temporarily "trapped" inside cells that are hungry for glucose - those activated by the brain stimulation - and remain there long enough for the detectors of a PET scanner to pick up the radioactive signal, even after the animals are anesthetized to ensure they stay still for scanning. But because the animals were awake and moving when the tracer was injected and the brain cells were being stimulated, the scans reveal what parts of the brain were activated (or deactivated) under those conditions, giving scientists important information about how those brain circuits function and correlate with the animals' behaviors.

"In this paper, we wanted to stimulate the nucleus accumbens, a key part of the brain involved in reward that is very important to understanding drug addiction," Thanos said. "We wanted to activate the cells in that area and see which brain circuits were activated and deactivated in response."

The scientists used the technique to trace activation and deactivation in number of key pathways, and confirmed their results with other analysis techniques.

The method can reveal even more precise effects.

"If we want to know more about the role played by specific types of receptors - say the dopamine D1 or D2 receptors involved in processing reward - we could tailor the light-sensitive protein probe to specifically stimulate one or the other to tease out those effects," he said.

Another important aspect is that the technique does not require the scientists to identify in advance the regions of the brain they want to investigate, but instead provides candidate brain regions involved anywhere in the brain - even regions not well understood.

"We look at the whole brain," Thanos said. "We take the PET images and co-register them with anatomical maps produced with magnetic resonance imaging (MRI), and use statistical techniques to do comparisons voxel by voxel. That allows us to identify which areas are more or less activated under the conditions we are exploring without any prior bias about what regions should be showing effects."

After they see a statistically significant effect, they use the MRI maps to identify the locations of those particular voxels to see what brain regions they are in.

"This opens it up to seeing an effect in any region in the brain - even parts where you would not expect or think to look - which could be a key to new discoveries," he said.

This work was supported by the intramural program at NIAAA as well as grants AA11034, AA07574, AA07611. Additional co-authors include: Lisa Robison and Ronald Kim, Stony Brook University; Eric J. Nestler and Michael Michaelides, Mount Sinai School of Medicine; Mary-Kay Lobo, University of Maryland School of Medicine; and Nora D. Volkow, NIAAA.

Scientific paper: "Mapping Brain Metabolic Connectivity in Awake Rats with ?PET and Optogenetic Stimulation"

An electronic version of this news release is available online

Media contacts: Karen McNulty Walsh, 631 344-8350, kmcnulty@bnl.gov or Peter A. Genzer, 631 344-3174, genzer@bnl.gov

***
Sidebar: Brookhaven and 18FDG
^18FDG is chemistry shorthand for 2-deoxy-2-[^18F]fluoro-D-glucose. It was originally synthesized at Brookhaven Lab in 1976, and is now the world's most widely used radiotracer for cancer diagnosis. In ^18FDG, a radioactive form of fluorine (^18F) takes the place of a hydrogen atom in a molecule that is very similar to glucose. When injected into the bloodstream, ^18FDG travels to wherever glucose (energy) is being used. As the radioactive ^18F atoms decay, they emit particles called positrons, identical to electrons but opposite in charge. When positrons and ordinary electrons interact, they produce back-to-back gamma rays. These signals, picked up by the circular array of detectors of a positron emission tomography (PET) scanner, can be used to identify the position of the original ^18F atom and create pictures of its location within the body. By tracking the tracer over time, scientists can monitor site-specific metabolic activity under a variety of conditions. MORE: http://www.bnl.gov/newsroom/news.php?a=11461
***
One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry, and government researchers. Brookhaven is operated and managed for DOE's Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation of the State University of New York, for and on behalf of Stony Brook University, the largest academic user of Laboratory facilities; and Battelle Memorial Institute, a nonprofit, applied science and technology organization. Visit Brookhaven Lab's electronic newsroom for links, news archives, graphics, and more (http://www.bnl.gov/newsroom) or follow Brookhaven Lab on Twitter (http://twitter.com/BrookhavenLab).

Karen McNulty Walsh | Newswise
Further information:
http://www.bnl.gov

More articles from Medical Engineering:

nachricht PET identifies which prostate cancer patients can benefit from salvage radiation treatment
05.12.2017 | Society of Nuclear Medicine and Molecular Imaging

nachricht Designing a golden nanopill
01.12.2017 | University of Texas at Austin, Texas Advanced Computing Center

All articles from Medical Engineering >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>