Study Shows Power of Gamma Augmentation as Potential Approach to Combat Depression

A new study in mice and rats, led by researchers at New York University’s Grossmann School of Medicine and Szeged University in Hungary, finds that restoring specific signals in brain regions that process odors can combat depression. I was.

Published online May 9 in the journal neuron, the research findings revolve around nerve cells, also called neurons, that “fire,” or emit electrical signals, to transmit information. Recent researchers have found that effective communication between brain regions requires groups of neurons to synchronize activity patterns with joint silence and subsequent oscillations of joint activity. One such rhythm, called gamma, repeats more than 30 times per second and is an important timing pattern for encoding complex information that may contain emotion.

The causes of depression are not well understood, but previous studies have shown that alterations in gamma oscillations are reflected as electrophysiological markers of disease in brain regions that govern olfaction, and that olfaction is also linked to emotion. . These areas include the olfactory bulbs adjacent to the nasal cavity. The olfactory bulb is believed to be the source and conductor of gamma oscillations throughout the brain.

To test this theory, the authors of the current study used genetic and cell signaling techniques to shut down olfactory bulb function in study rodents and associated increases in depression-like behavior in subjects. and then reversed these behaviors using a device that boosts gamma signals in the brain at a natural pace.

Our experiments reveal a mechanistic link between lack of gamma activity and behavioral depression in mouse and rat models of depression, suggesting an olfactory and connected cerebral cortex similar to that seen in depressed patients. Signal changes in the limbic system were seen. This study demonstrates the power of gamma-enhancement as a potential approach to combat depression and anxiety when available drugs are ineffective.”

Antal Berenyi, MD, PhD, Corresponding study authors, Adjunct Assistant Professor, Department of Neuroscience and Physiology, NYU Langone Health

Major depressive disorder is a common, severe mental illness that often resists medication, researchers say. The prevalence of the condition has increased dramatically since the start of the pandemic, with an estimated over 53 million new cases reported.

gamma waves associated with emotions

Disease-causing alterations in the timing and intensity of gamma signals from the olfactory bulb to other brain regions of the limbic system, such as the piriform cortex and hippocampus, can be caused by infection, trauma, or drugs, and can be associated with emotions. may change. However, the research team is not sure why. One theory is that depression does not occur within the olfactory bulb, but through changes in outgoing gamma patterns to other brain targets.

Bulb removal represents an older animal model for studying major depression, but the process can cause structural damage and cloud researchers’ view of disease mechanisms. To do so, the current research team designed a reversible method that starts with a single engineered DNA strand encapsulated in a harmless virus. When injected into neurons in the olfactory bulb of rodents, the DNA caused them to build specific protein receptors on the surface of the cells.

This allowed researchers to inject drugs into rodents. The drug spreads throughout the system, but only shuts down neurons in the bulb that are designed to have receptors that are sensitive to the designed drug. We were able to switch off communication between brain regions in our partners. clarified.

To show the effects of the loss of gamma oscillations in the olfactory bulb, the research team used several standard rodent tests, including a measure of anxiety, one of the main symptoms of depression. Recognizing that animal models of human mental states are limited in the field, a battery of tests is used to measure depressive behaviors that have proven useful over time. I’m here.

Specifically, the test looked at the amount of time animals spent in open space, a measure of anxiety. A measure of despair, whether they stopped swimming early when submerged. Whether or not they have stopped drinking sugar water, a sign that they are not very happy with things. Whether or not you refuse to enter the maze is a sign that you are avoiding stressful situations.

The researchers then used a custom-made device that recorded natural gamma oscillations from the olfactory bulb and sent these pacing signals back to the rodent brain as closed-loop electrical stimulation. This device could either suppress or amplify gamma rays in healthy animals. Suppression of gamma oscillations in the olfactory lobe caused behavior similar to depression in humans. Furthermore, sending amplified olfactory bulb signals back to the brains of depressed rats restored normal gamma function in the limbic system, reducing depressive behavior by 40% and returning it to near normal.

“No one yet knows how gamma wave firing patterns translate into emotions,” said Biggs, senior professor of neuroscience in the Department of Neuroscience and Physiology and faculty member of the Institute of Neuroscience. Study author György Buzsáki, MD, Ph.D. “As behavior changes, we will move forward to better understand this link in bulbs and the regions they connect to.”

Along with Dr. Berényi and Dr. Buzsáki, the study was led by Orrin Devinsky, MD, professor of neurology at NYU Langone and director of the Comprehensive Epilepsy Center. Dr. Bereni is also the principal investigator of the Momentum Oscillating Neural Network Research Group at the Department of Physiology, University of Szeged, Hungary, and the authors of the original study, Kung Li and Yuichi Takeuchi, and authors Ziare Wang, Levente Gellert and Livia Barsai. , Liseth Pedraza, Annette Nagy, Gabor Kozark, Jenzy Horvat, Gabriela Kakesi, Magor Lorinz. Study authors Shinya Nakai and Masahiro Osawa are from the Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan. Takeuchi is also a faculty member at the Department of Physiology, Graduate School of Medicine, Osaka City University and Faculty of Pharmaceutical Sciences, Hokkaido University. Additional study authors were Shigeki Kato and Kazuto Kobayashi, members of the Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University, Japan.

Funding for this study was provided through a grant from the Momentum II program of the Hungarian Academy of Sciences. Hungarian National Research, Development and Innovation Agency. Ministry of Innovation, Hungary; Ministry of Human Capabilities, Hungary. Hungarian Scientific Research Fund; Hungarian Brain Research Program. European Union Horizon 2020 research and innovation program. Japan Society for the Promotion of Science. Ministry of Education, Culture, Sports, Science and Technology of Japan. Japan Agency for Medical Research and Development. Additional support was provided by the Kanae Medical Foundation, the Nippon Life Science Foundation, the Takeda Science Foundation, the Japanese Neural Network Society, and the János Bolyai Fellowship.