MSGID: 1:317/3 645b1de1   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Potential found to counter depression by restoring key brain rhythm   
    Study proposes role for gamma oscillations in future treatment    
      
     Date:   
         May 9, 2023   
     Source:   
         NYU Langone Health / NYU Grossman School of Medicine   
     Summary:   
         A new study in mice and rats found that restoring certain signals   
         in a brain region that processes smells countered depression.   
      
      
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   Led by researchers from NYU Grossman School of Medicine and University   
   of Szeged in Hungary, a new study in mice and rats found that restoring   
   certain signals in a brain region that processes smells countered   
   depression.   
      
   Publishing in the journal Neuron online May 9, the study results revolve   
   around nerve cells (neurons), which "fire" -- or emit electrical signals   
   -- to transmit information. Researchers in recent years discovered   
   that effective communication between brain regions requires groups of   
   neurons to synchronize their activity patterns in repetitive periods   
   (oscillations) of joint silence followed by joint activity. One such   
   rhythm, called "gamma," repeats about 30 times or more in a second, and   
   is an important timing pattern for the encoding of complex information,   
   potentially including emotions.   
      
   Although its causes remain poorly understood, depression is reflected   
   in gamma oscillation changes, according to past studies, as an   
   electrophysiological marker of the disease in brain regions that manage   
   the sense of smell, which have also been tied to emotions. These regions   
   include the olfactory bulb adjacent to the nasal cavity, which is thought   
   to be a source and "conductor" of brain-wide gamma oscillations.   
      
   To test this theory, the current study authors shut down the function of   
   the bulb using genetic and cell signaling techniques, observed a related   
   increase of depression-like behaviors in study rodents, and then reversed   
   these behaviors using a device that boosted gamma signals of the brain   
   at their natural pace.   
      
   "Our experiments revealed a mechanistic link between deficient gamma   
   activity and behavioral decline in mice and rat models of depression,   
   with the signal changes in the olfactory and connected limbic systems   
   similar to those seen in depressed patients," says corresponding study   
   author Antal Bere'nyi, MD, PhD, adjunct assistant professor in the   
   Department of Neuroscience and Physiology at NYU Langone Health. "This   
   work demonstrates the power of gamma-enhancement as a potential approach   
   for countering depression and anxiety in cases where available medications   
   are not effective."  Major depressive disorder is a common, severe   
   psychiatric illness often resistant to drug therapy, the researchers   
   say. The prevalence of the condition has dramatically increased since   
   the start of the pandemic, with more than 53 million new cases estimated.   
      
   Gamma Waves Linked to Emotions Disease-causing changes in the timing   
   and strength of gamma signals, potentially caused by infections,   
   trauma, or drugs, from the olfactory bulb to other brain regions of the   
   limbic system, such as the piriform cortex and hippocampus, may alter   
   emotions. However, the research team is not sure why. In one theory,   
   depression arises, not within the olfactory bulb, but in changes to its   
   outgoing gamma patterns to other brain targets.   
      
   Removal of the bulb represents an older animal model for the study of   
   major depression, but the process causes structural damage that may cloud   
   researchers' view of disease mechanisms. Thus, the current research team   
   designed a reversible method to avert damage, starting with a single,   
   engineered strand of DNA encapsulated in a harmless virus, which when   
   injected into neurons in the olfactory bulbs of rodents caused the cells   
   to build certain protein receptors on their surfaces.   
      
   This let the researchers inject the rodents with a drug, which spread   
   system- wide, but only shut down the neurons in the bulb that had   
   been engineered to have the designed drug-sensitive receptors. This   
   way the investigators could selectively and reversibly switch off   
   the communication between the bulb partner brain regions. These tests   
   revealed that chronic suppression of olfactory bulb signals, including   
   gamma, not only induced depressive behaviors during the intervention,   
   but fordays afterward.   
      
   To show the effect of the loss of gamma oscillation in the olfactory bulb,   
   the team used several standard rodent tests of depression, including   
   measures of the anxiety that is one of its main symptoms. The field   
   recognizes that animal models of human psychiatric conditions will be   
   limited, and so uses a battery of tests to measure depressed behaviors   
   that have proven useful over time.   
      
   Specifically, the tests looked at how long animals would spend in an open   
   space (a measure of anxiety), whether they stopped swimming earlier when   
   submerged (measures despair), whether they stopped drinking sugar water   
   (took less pleasure in things), and whether they refused to enter a maze   
   (avoided stressful situations).   
      
   The researchers next used a custom-made device that recorded the   
   natural gamma oscillations from the olfactory bulb, and sent those   
   paced signals back into the rodents' brains as closed-loop electrical   
   stimulation. The device was able to suppress gamma in healthy animals   
   or amplify it. Suppression of gamma oscillations in the olfactory lobe   
   induced behaviors resembling depression in humans. In addition, feeding   
   an amplified olfactory bulb signal back into the brains of depressed   
   rats restored normal gamma function in the limbic system, and reduced   
   the depressive behaviors by 40 percent (almost to normal).   
      
   "No one yet knows how the firing patterns of gamma waves are converted   
   into emotions," says senior study author Gyo"rgy Buzsa'ki, MD, PhD,   
   the Biggs Professor in the Department of Neuroscience and Physiology   
   at NYU Langone Health and a faculty member in its Neuroscience   
   Institute. "Moving forward, we will be working to better understand   
   this link in the bulb, and in the regions it connects to, as behavior   
   changes."  Along with Bere'nyi and Buzsa'ki, the study was led by Orrin   
   Devinsky, MD, professor in the in Department of Neurology at NYU Langone,   
   and director of its Comprehensive Epilepsy Center. Bere'nyi is also   
   principal investigator of the Momentum Oscillatory Neuronal Networks   
   Research Group, Department of Physiology at the University of Szeged   
   in Hungary, along with first study authors Qun Li and Yuichi Takeuchi,   
   and authors Jiale Wang, Levente Gelle'rt, Livia Barcsai, Lizeth Pedraza,   
   Anett Nagy, Ga'bor Koza'k, Gyo"ngyi Horva'th, Gabriella Ke'kesi and   
   Magor L?rincz. Study authors Shinya Nakai and Masahiro Ohsawa are with   
   the Department of Neuro-pharmacology, Graduate School of Pharmaceutical   
   Sciences, at Nagoya City University in Japan. Takeuchi is also faculty   
   in the Department of Physiology, Osaka City University Graduate School   
   of Medicine and Faculty of Pharmaceutical Sciences, Hokkaido University   
   in Japan. Also study authors were Shigeki Kato and Kazuto Kobayashi   
   Department of Molecular Genetics, Institute of Biomedical Sciences at   
   Fukushima Medical University School of Medicine in Japan.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Nervous_System # Psychology_Research #   
                   Mental_Health_Research # Diseases_and_Conditions   
             o Mind_&_Brain   
                   # Neuroscience # Depression # Disorders_and_Syndromes   
                   # Psychiatry   
       * RELATED_TERMS   
             o Psychedelic_drug o Mouse o Multiple_sclerosis o   
             Postpartum_depression o Psycholinguistics o Thalamus o   
             House_mouse o Hypothalamus   
      
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   Story Source: Materials provided by   
   NYU_Langone_Health_/_NYU_Grossman_School_of_Medicine.   
      
   Note: Content may be edited for style and length.   
      
      
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   Journal Reference:   
      1. Qun Li, Yuichi Takeuchi, Jiale Wang, Levente Gelle'rt, Livia   
      Barcsai,   
         Lizeth K. Pedraza, Anett J. Nagy, Ga'bor Koza'k, Shinya Nakai,   
         Shigeki Kato, Kazuto Kobayashi, Masahiro Ohsawa, Gyo"ngyi Horva'th,   
         Gabriella Ke'kesi, Magor L. Lőrincz, Orrin Devinsky, Gyo"rgy   
         Buzsa'ki, Antal Bere'nyi. Reinstating olfactory bulb-derived limbic   
         gamma oscillations alleviates depression-like behavioral deficits   
         in rodents. Neuron, 2023; DOI: 10.1016/j.neuron.2023.04.013   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/05/230509122011.htm   
      
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