Temporary disconnects shed light on long-term brain dysfunction

Yizhar is particularly interested in the long-distance communications between nerve cells in different areas of the brain.

Rambam Medical Center campus contains the National Poison Control Center  (NPCC) (photo credit: Courtesy)
Rambam Medical Center campus contains the National Poison Control Center (NPCC)
(photo credit: Courtesy)
Will we ever be able to understand the cacophonous chatter taking place between the 80 million neurons in our brains? Dr. Ofer Yizhar and his group in the Weizmann Institute of Science’s neurobiology department have taken a large step in this direction with a new research method that can provide scientists with targeted control over vital parts of the brain’s communications.
Yizhar works in the relatively new field of optogenetics, in which scientists use genetic engineering and laser light in thin optical fibers to investigate the living brain. With these tools, scientists can modulate and control the activities of nerve circuits in the brain, and thus begin to unravel the networks of links and nodes in the brain’s communications systems.
Yizhar is particularly interested in the long-distance communications between nerve cells in different areas of the brain.
“The coordination between different brain systems is vital to the normal functioning of the brain. If we can understand the extended lines of communication between cells that are in the different regions of the brain – some of them quite far from one another,” said Yizhar, “we might be able, in the future, to understand the changes that take place in the brain in diseases such as depression, anxiety and schizophrenia. Because we do not have an understanding of these diseases on a functional level, we are sorely lacking good ways to treat them.”
Optogenetics involves inserting a gene for a light-sensitive protein into the neurons, using a modified virus. These neurons then become activated when light is focused on them through the thin optical fibers. Yizhar and his team established a method that allows them to zoom in on a particular part of the brain’s network: the “communications cables” that link up the entire brain. These “cables” are the axons – thin extensions of the nerve cells that carry electric pulses from the cells’ centers.
Some axons are relatively short and linked to nearby neurons, but others can be lengthy, reaching out to distant regions of the brain.
In the new study, which was recently published in Nature Neuroscience, the team (led by doctoral student Mathias Mahn) showed that optogenetic techniques can be used to temporarily silence these long-range axons, effectively leading to a reversible “disconnect” between two distant brain nodes.
By observing what happens when crucial connections are disabled, the researchers were able to begin to filling in the picture of the axons’ role in the brain’s internal conversation. Since mental and neurological diseases are often thought to result from changes in long-range brain connectivity, these studies could contribute to a better understanding of the mechanisms behind health and disease in the brain.
“The research led us to a deeper understanding of the unique properties of the axons and synapses that form the connections between neurons,” explained Yizhar.
“We were able to uncover the responses of axons to various optogenetic manipulations.
Understanding these differences will be crucial to unraveling the mechanisms for long-distance communication in the brain.”
Doctors and researchers at Rambam Medical Center in Haifa will now be able to better diagnose and monitor diseases at a functional level with GE Healthcare’s next-generation SPECT/CT system, called Discovery NM/CT 670 CZT. The device is the world’s first general purpose, ultrahigh resolution SPECT/CT imaging system, with a new digital detector powered by cadmium zinc telluride (CZT) technology.
This is one of the biggest nuclear medicine technological breakthroughs since the introduction of the first general purpose gamma camera designed by Hal Anger in 1957.
SPECT/CT exams are performed to assess the functionality of organs and play a key role in the diagnosis and monitoring of a multitude of diseases. GE Healthcare’s new system is equipped with CZT technology that enables direct conversion of photons into a digital signal, therefore making the technology more efficient. Until now, CZT technology has been limited to organ-dedicated devices, whereas Discovery NM/ CT 670 CZT makes it possible to perform exams on every organ, including wholebody exams, thus improving clinical efficacy.
Doctors will be able to detect smaller lesions and quantify them more accurately, thanks to the increased spatial and contrast resolution.
Having the ability to complete multiple scans in a single visit and reduce the dose injected or the scan time by 50 percent will improve patient experience. Optimizing the duration of the exams or the injected dose represents not only an improvement for the patient experience, but also increases the operational and financial efficiency of hospitals.
“We are looking forward to evaluating the clinical benefits of the technological capabilities of the new device, specifically those based on the physical properties of the new CZT solid state detectors. Based the lab data, we believe we may be able to significantly improve our clinical performance to a level that is not easy to reach with the currently available conventional devices,” explained Prof. Ora Israel, director of the nuclear medicine at Rambam.
Patients who have physical limitations will particularly benefit from the new system, said Israel.
“One example is cardiac SPECT exams that require the patient to hold his arms above his shoulders for the entire exam, very tightly to the head to permit the detectors to rotate closely around the chest for the best image quality. For patients with arm or shoulder pain this can be extremely painful and possibly intolerable for the duration of the scan.”