Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

High-resolution mapping technique uncovers underlying circuit architecture of the brain

28.06.2013
Joint Salk-Gladstone study to help scientists decode circuitry that guides brain function

The power of the brain lies in its trillions of intercellular connections, called synapses that together form complex neural "networks." While neuroscientists have long sought to map these individual connections to see how they influence specific brain functions, traditional techniques have been unsuccessful.


The microscope image shows nerve cells in the mouse brain that have been labeled with a modified rabies virus. These cells send direct connections to striatum, a region of the brain that regulates voluntary movement. The striatum is disrupted in degenerative disorders such as Parkinson's disease and Huntington's disease.

Credit: Courtesy of Nicholas Wall, Salk Institute for Biological Studies

Now, scientists at the Salk Institute and the Gladstone Institutes, using an innovative brain- tracing technique, have found a way to untangle these networks. These findings offer new insight into how specific brain regions connect to each other, while also revealing clues as to what may happen, neuron by neuron, when these connections are disrupted.

In the latest issue of Neuron, a team led by Edward Callaway, a Salk professor and holder of the Audrey Geisel Chair in Biomedical Science, and Anatol Kreitzer, a Gladstone investigator, combined mouse models with a sophisticated tracing technique---- known as the monosynaptic rabies virus system---- to assemble brain-wide maps of neurons that connect with the basal ganglia, a region of the brain that is involved in movement and decision-making. Developing a detailed anatomical understanding of this region is important as it could inform research into disorders that can be traced to basal ganglia dysfunction, including both Parkinson's disease and Huntington's disease.

"The monosynaptic rabies virus approach---- pioneered by Dr. Callaway---- is ingenious in the exquisite precision that it offers compared with previous methods, which were messier with a much lower resolution," explained Kreitzer, who is also an assistant professor of neurology and physiology at the University of California, San Francisco, with which Gladstone is affiliated. "In this paper, we took the approach one step further by activating the tracer genetically, which ensures that it is only turned on in specific neurons in the basal ganglia. This is a huge leap forward technologically, as we can be sure that we're following only the networks that connect to particular kinds of cells in the basal ganglia from other parts of the brain."

At Gladstone, Kreitzer focuses his research on the basal ganglia as it relates to Parkinson's. Last year, he and his team published research that revealed clues to the relationship between two types of neurons found in the region-and how they guide both movement and decision-making. These two types, called direct-pathway medium spiny neurons (dMSNs) and indirect-pathway medium spiny neurons (iMSNs), act as opposing forces. dMSNs initiate movement, like the gas pedal, and iMSNs inhibit movement, like the brake. The latest research from the Kreitzer lab further found that these two types are also involved in behavior, specifically decision-making, and that dysfunctions in dMSNs and iMSNs are associated with addictive and depressive behaviors, respectively. These findings were important because they provided a link between the physical neuronal degeneration seen in movement disorders, such as Parkinson's, and some of the disease's behavioral aspects. But this study still left many questions unanswered.

"For example, while that study and others like it revealed the roles of dMSNs and iMSNs in movement and behavior, we knew very little about how other brain regions influenced the function of these two neuron types," said Nicholas Wall, a Salk Institute postdoctoral fellow and the paper's first author. "The monosynaptic rabies virus system helps us address that question."

The system, originally developed in 2007 and refined by Wall and Callaway for targeting specific cell types in 2010, uses a modified version of the rabies virus to "infect" a brain region, which in turn targets neurons that are connected to it. When the system was applied in genetic mouse models, the team could see specifically how sensory, motor, and reward structures in the brain connected to MSNs in the basal ganglia. What they found was surprising.

"We noticed that some regions showed a preference for transmitting to dMSNs vs. iMSNs, and vice versa," said Kreitzer. "For example, neurons residing in the brain's motor cortex tended to favor iMSNs, while neurons in the sensory and limbic systems preferred dMSNs. This fine-scale organization, which would have been virtually impossible to observe using traditional techniques, allows us to predict the distinct roles of these two neuronal types."

"These initial results should be treated as a resource not only for decoding how this network guides the vast array of very distinct brain functions, but also how dysfunctions in different parts of this network can lead to different neurological conditions," said Callaway. "If we can use the rabies virus system to pinpoint distinct network disruptions in distinct types of disease, we could significantly improve our understanding of these disease's underlying molecular mechanisms-and get even closer to developing solutions for them."

This research was supported by the Gatsby Charitable Foundation and the National Institutes of Health.

Kat Kearney | EurekAlert!
Further information:
http://www.salk.edu

More articles from Life Sciences:

nachricht Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology

nachricht Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Osaka university researchers make the slipperiest surfaces adhesive

18.10.2017 | Materials Sciences

Space radiation won't stop NASA's human exploration

18.10.2017 | Physics and Astronomy

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>