New Methods in Brain Scans to Examine Running Rats and Flying Bats
Researchers from the U.S. Department of Energy’s Brookhaven National Laboratory and Thomas Jefferson National Accelerator Facility, Oak Ridge National Laboratory, Johns Hopkins Medical School, the University of Maryland, and Weizmann Institute’s Neurobiology Department have all developed new and improved brain scanning techniques. These new methods allow scientists to monitor brain activity in fully-awake, moving animals.
At Brookhaven, researchers combined light-activated proteins that stimulate specific brain cells, a technique known as optogenetics, with positron emission tomography (PET) to observe the effects of stimulation throughout the entire brain. Their paper in the Journal of Neuroscience describes this method, which will allow researchers to map exactly which neurological pathways are activated or deactivated downstream by stimulation in specific brain areas. Hopefully, following these pathways will enable researchers to correlate the brain activity with observed behaviors or certain symptoms of disease.
Three markers on the head of a mouse enable the AwakeSPECT system to obtain functional images of the brain of a conscious mouse as it moves around. (Credit: Image courtesy of DOE/Thomas Jefferson National Accelerator Facility)
Scientists at Oak Ridge used dynamic imaging in mice to examine changes in brain chemistry caused by disease or application of a drug. They hope this research tool will be used to develop better disease diagnostics as well as better treatments. The newest aspect of this study, however, is that unlike most nuclear imaging studies where laboratory mice are drugged or kept in place so that their brains can be studied, the new technique allows for moving subjects. The researchers from Jefferson Lab, Oak Ridge, Johns Hopkins and Maryland used their new system to obtain functional images of the brains of conscious mice that were free to move. The system, called AwakeSPECT (Awake Single-Photon Emission Computed Tomography), was then used to examine the effects of anesthesia on the action of a dopamine transporter in the mouse brain for the first time. These types of dopamine transporter imaging compounds are used for Alzheimer’s, dementia and Parkinson’s disease studies. The technique entails injection of a radionuclide, which gathers in targeted areas of the brain. The radionuclide emits gamma rays that are detected in separate scans from many different angles, all of which are combined by an algorithm to produce a three-dimensional image.
Martin Pomper led a group of researchers at Johns Hopkins Medical School to conduct the first mouse imaging studies with the new system. Their study showed that AwakeSPECT can be used to obtain detailed, functional images of the brain in a conscious mouse that was able to move freely around in an enclosed space. “We’ve shown the technology works. Now, you just have to make it a tool that more people will readily use” says Jefferson Lab’s Drew Weisenberger, who led the multi-institutional collaboration that created the novel technique.
One area of active research that would benefit from such imaging techniques is the question of how animals orient themselves in space. Existing experiments have all looked at how animals move around in two-dimensional settings and they have made the important discovery of place cells, neurons located in the hippocampus responsive to spatial orientation. Populations of place cells working together can produce full representations of an animal’s environment, the only problem being that in the real world animals have to navigate in three dimensions unlike the laboratory experiments. That’s why Dr. Nachum Ulanovsky of the Weizmann’s Institute’s Neurobiology Department chose to study the Egyptian fruit bat to look at how three-dimensional space is perceived in mammalian brains for the first time. His research used a miniaturized neural-telemetry system developed especially for this task, which enabled the measurement of single brain cells during flight. The activity of the hippocampal neurons in the bats’ brains showed that the representation of three-dimensional space is just like in two dimensions: each place cell is responsible for identifying a particular spatial area in space and sends an electrical signal when the bat is located in that area. The population of place cells provides full coverage of the particular area, say a cave, left, right, forward, back, up and down.
These results give new insights into navigation, spatial memory and spatial perception, all basic functions of the mammalian brain. The study’s success is due to the development of the technology that allowed looking into the brain of a flying animal. Single cell measurement is only the first step, looking at neural circuits can reveal much more about how these place cell representations are then used in conjunction with other brain areas resulting in the behavior we see. Development of new brain imaging techniques continues to provide a more complete understanding of basic human and animal behaviors, and hopefully one day will lead to a full understanding of the human brain.
-Leo Shapiro
Sources:
Lights, Chemistry, Action: New Method for Mapping Brain Activity – ScienceDaily
System Provides Clear Brain Scans of Awake, Unrestrained Mice – ScienceDaily
Neural Activity in Bats Measured In-Flight – ScienceDaily
