Restoring Gamma Wave Signals Could Counteract Depression

Summary: Restoring certain signals in the region of the brain that processes smell can counteract depression, a new study has found. The study reported that the timing and strength of gamma signals in the olfactory bulb can alter emotions.

The findings could provide a potential new approach to tackling depression and anxiety when medication isn’t effective. Researchers warn that more studies are needed to understand the link between gamma wave triggering patterns and emotions.

Highlights:

1. Gamma oscillation changes have been shown to be an electrophysiological marker of depression in brain regions that handle smell, which have also been linked to emotions.
2. The researchers used a reversible method to cut off communication between the olfactory bulb and partner brain regions, which induces depressive behaviors in mice and rats.
3. Researchers used a device to restore the brain’s gamma signals to their natural rhythm, which reduced depressive behaviors by 40%.

Source: NYU Langone

Led by researchers from NYU Grossman School of Medicine and the University of Szeged in Hungary, a new study in mice and rats found that restoring certain signals in a region of the brain that processes smells thwarts depression .

Publication in the journal neuron online May 9, the study’s findings revolve around nerve cells (neurons), which “trigger” — or emit electrical signals — to transmit information.

Researchers in recent years have discovered that effective communication between brain regions requires groups of neurons to synchronize their patterns of activity in repetitive periods (oscillations) of joint silence followed by joint activity.

One of these rhythms, called “gamma,” repeats about 30 or more times per second and is an important timing pattern for encoding complex information, which can include emotion.

Although its causes remain poorly understood, depression is reflected in gamma oscillation changes, according to previous studies, as an electrophysiological marker of disease in brain regions that manage smell, which have also been linked to emotions. These regions include the olfactory bulb adjacent to the nasal cavity, which is thought to be a source and “driver” of brain-wide gamma oscillations.

To test this theory, the authors of the current study shut down light bulb function using genetic and cellular signaling techniques, observed a related increase in depression-like behaviors in the study rodents, then reversed these behaviors using a device that amplified the brain’s gamma signals at its natural rate.

“Our experiments revealed a mechanistic link between deficient gamma activity and behavioral decline in mice and rat models of depression, with signaling changes in olfactory and connected limbic systems similar to those seen in depressed patients,” says the study’s corresponding author, Antal Berényi, 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 to addressing depression and anxiety in cases where available medications are not effective.”

According to the researchers, major depressive disorder is a serious and common psychiatric illness that is often resistant to drug therapy. The prevalence of the disease has increased significantly since the start of the pandemic, with more than 53 million new cases estimated.

Gamma waves related to emotions

Pathogenic 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, can alter the emotions.

However, the research team does not know why. According to one theory, depression arises, not in the olfactory bulb, but in changes in its outgoing gamma patterns to other brain targets.

Bulb removal represents an older animal model for studying major depression, but the process causes structural damage that can cloud researchers’ view of disease mechanisms.

So the current research team devised a reversible method to avoid damage, starting with a single strand of DNA encapsulated in a harmless virus, which, when injected into the neurons of rodent olfactory bulbs, has caused cells to build certain protein receptors on their surfaces.

This allowed the researchers to inject the rodents with a drug, which spread throughout the system, but only shut down the bulb neurons that had been engineered to have the engineered drug-responsive receptors. In this way, the researchers were able to selectively and reversibly deactivate communication between the bulb’s partner brain regions.

These tests revealed that chronic suppression of olfactory bulb signals, including gamma, not only induced depressive behaviors during the procedure, but for days after.

To show the effect of the loss of gamma oscillation in the olfactory bulb, the team used several standard tests for depression in rodents, including measures of anxiety which is one of its main symptoms. The field recognizes that animal models of human psychiatric disorders will be limited and therefore uses a battery of tests to measure depressive behaviors that have proven useful over time.

Specifically, the tests looked at how long the animals would spend in an open space (a measure of anxiety), whether they had stopped swimming sooner when submerged (a measure of desperation), whether they had stopped drinking sugar water (took less pleasure in things) and if they refused to enter a maze (avoided stressful situations).

The researchers then used a custom-made device that recorded the natural gamma oscillations of the olfactory bulb and fed those rhythmic 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 induces depression-like behaviors in humans. Moreover, reintroducing an amplified signal from the olfactory bulb into the brains of depressed rats restored normal gamma function in the limbic system and reduced depressive behaviors by 40% (near normal).

“No one yet knows how gamma wave triggering patterns are converted into emotions,” says study lead author György Buzsáki, MD, PhD, Biggs Professor in the Department of Neuroscience and Physiology at NYU Langone Health and Fellow of the faculty of its neuroscience department. Institute.

“Going forward, we will work to better understand this link in the bulb and in the regions to which it connects, as the behavior changes.”

Funding: Funding for the study was provided by grants from the Momentum II program of the Hungarian Academy of Sciences, the Hungarian National Office for Research, Development and Innovation, the Hungarian Ministry of Innovation and of Technology, the Hungarian Ministry of Human Capacities, the Hungarian Office for Scientific Research Fund, the Hungarian Brain Research Program, the European Union’s Horizon 2020 Research and Innovation Program, Japanese Society for the promotion of science, the Japanese Ministry of Education, Culture, Sports, Science and Technology, the Japanese Agency for Medical Research and Development, as well as by the support of the Foundation Kanae for the Advancement of Medical Sciences, Life Science Foundation of Japan, Takeda Science Foundation, Japanese Neural Network Society, and János Bólyai Fellowship.

About this depression research

Author: Greg Williams
Source: NYU Langone
Contact: Greg Williams – New York University Langone
Picture: Image is credited to Neuroscience News

Original research: Free access.
“Restoration of limbic gamma oscillations derived from the olfactory bulb alleviates 1 depressionby Antal Berényi et al. neuron

Abstract

Restoration of limbic gamma oscillations derived from the olfactory bulb alleviates 1 depression

Strong points

• Suppression of OB or OB-PirC pathway decreases gamma and induces depressive symptoms
• Anti-phase closed-loop stimulation of gamma PirC resembles depressive symptoms
• Ketamine improves depressive symptoms induced by anti-phase gamma stimulation
• In-phase gamma stimulation alleviates LPS-induced symptoms

Summary

Although the etiology of major depressive disorder remains poorly understood, reduction in gamma oscillations is an emerging biomarker. Olfactory bulbectomy, an established model of depression that reduces limbic gamma oscillations, suffers from nonspecific effects of structural damage.

Here, we show that transient functional suppression of olfactory bulb neurons or their piriform cortex efferents decreased gamma oscillation power in limbic areas and induced depression-like behaviors in rodents.

Enhancing the transmission of gamma oscillations from the olfactory bulb to limbic structures by closed-loop electrical neuromodulation attenuated these behaviors.

In contrast, reduction of gamma transmission by anti-phase closed-loop stimulation enhanced depression-like behaviors in naïve animals. These induced behaviors were reversed by ketamine treatment which restored limbic gamma potency.

Taken together, our results reveal a causal link between gamma limbic oscillations and depression-like behaviors in rodents. Interfering with these endogenous rhythms can affect the behaviors of rodent models of depression, suggesting that restoring gamma oscillations can alleviate depressive symptoms.