summary: A new study found that restoring specific signals in brain regions that process odors can combat depression. It is reported that there are
This finding may provide a potential new approach to combat depression and anxiety when medication is ineffective. He warns that further research is needed to understand the
Important facts:
- Changes in gamma oscillations have been found to be electrophysiological markers of depression in brain regions that govern olfaction, which is also associated with emotion.
- Researchers used a reversible method to turn off communication between the olfactory bulb and partner brain regions to induce depressive behavior in mice and rats.
- Researchers used a device that restores the brain’s gamma signals at a natural pace and were able to reduce depressive behavior by 40%.
sauce: NYU Langone
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.
Publication in magazines neuron The findings, published online May 9, revolve around nerve cells (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 repeated periods (oscillations) of joint silence followed by joint activity. bottom.
One such rhythm, called ‘gamma’, repeats about 30 times or more per second and is an important timing pattern for encoding complex information that may contain emotion.
The cause is not well understood, but previous research has shown that depression is reflected in changes in gamma oscillations, electrophysiological markers of disease in brain regions that control smell, and is also linked to emotion. . These areas include the olfactory bulbs adjacent to the nasal cavity. It 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 bulb function and observed an associated increase in depression-like behavior in study rodents. and then reversed these behaviors using a device that boosts the gamma signal in the brain at a natural pace.
“Our experiments reveal a mechanistic link between a lack of gamma-ray activity and behavioral depression in depression models in mice and rats, suggesting that changes in olfactory and connected limbic signals are It was similar to what we see in depressed patients,” said corresponding study author Antal Berényi, MD. , PhD, adjunct assistant professor in the Department of Neuroscience and Physiology at NYU Langone Health.
“This study demonstrates the power of gamma-enhancing as a potential approach to combat depression and anxiety when available drugs are ineffective.”
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.
Therefore, the current research team designed a reversible method to avoid damage, starting with a single engineered DNA strand encapsulated in a harmless virus. When the virus was injected into neurons in the olfactory bulb of rodents, it caused the cells to build specific protein receptors. surface.
This allowed researchers to inject drugs into rodents. The drug spreads throughout the body, but only shuts down neurons in the bulb that are designed to have receptors that are sensitive to the designed drug. In this way, the researchers were able to selectively and reversibly turn off communication between the brain regions of the bulb partner.
These tests showed that chronic suppression of olfactory bulb signals, including gamma, not only induced depressive behavior during the intervention; A few days later.
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 included the amount of time animals spent in open space (a measure of anxiety), whether they stopped swimming early when submerged (a measure of despair), and whether they stopped drinking sugar water (a measure of despair). less fun), and they refused to enter the maze (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. Moreover, sending amplified olfactory bulb signals back to the depressed rat’s brain restored normal gamma function in the limbic system and reduced his depressive behavior by 40% (near normal).
“No one yet knows how gamma wave firing patterns are translated into emotions,” says Biggs, senior researcher and neuroscience faculty member in NYU Langone Health’s Department of Neuroscience and Physiology. Author György Buzsáki, M.D., said: Institute.
“As behavior changes, we will continue to work to better understand this link in bulbs and the regions they connect to.”
Funding: Funding for this research was provided through grants from the Momentum II Program of the Hungarian Academy of Sciences, the Hungarian National Agency for Research, Development and Innovation, the Hungarian Ministry of Innovation and Technology, the Hungarian Ministry of Human Resources, and the Hungarian Ministry of Scientific Research. Fund, Hungarian Brain Research Program, European Union Horizon 2020 Research Innovation Program, Japan Society for the Promotion of Science, Ministry of Education, Culture, Sports, Science and Technology, Japan Agency for Medical Research and Development, Kanae Foundation for the Promotion of Medical Science, Japan Life Science Foundation, Takeda Science Foundation, Japan Neuroscience It is also supported by the Circuit Society and the János Bólyai Fellowship.
About this Depression Research News
author: Greg Williams
sauce: NYU Langone
contact: Greg Williams – NYU Langone
image: Image credited to Neuroscience News
Original research: open access.
“Restoring limbic gamma oscillations from the olfactory bulb alleviates one depression” Antal Berényi et al. neuron
overview
Restoring limbic gamma oscillations from the olfactory bulb alleviates one depression
highlight
- Suppression of the OB or OB-PirC pathway reduces gamma and induces depressive symptoms
- Antiphase closed-loop stimulation of PirC gamma mimics depressive symptoms
- Ketamine ameliorates depressive symptoms induced by antiphase gamma stimulation
- In-phase gamma stimulation alleviated LPS-induced symptoms
summary
Although the etiology of major depressive disorder remains poorly understood, decreased gamma oscillations are an emerging biomarker. Olfactory bulbectomy, an established model of depression that reduces limbic gamma oscillations, suffers from the nonspecific effects of structural damage.
Here we show that transient functional inhibition of olfactory bulb neurons or their piriform corticoefferents reduced gamma oscillation power in limbic regions and induced depression-like behavior in rodents. increase.
Enhancing the transmission of gamma oscillations from the olfactory bulb to limbic structures through closed-loop electrical neuromodulation moderated these behaviors.
In contrast, silencing gamma-ray transmission by antiphase closed-loop stimulation enhanced depression-like behavior in naive animals. These evoked behaviors were neutralized by ketamine treatment, which restores limbic gamma power.
Taken together, our results reveal a causal link between limbic gamma oscillations and depression-like behavior in rodents. Disrupting these endogenous rhythms can affect behavior in rodent models of depression, suggesting that restoring gamma oscillations may alleviate symptoms of depression. increase.
