Key Facts: Fear Filter: The endocannabinoid 2-AG helps suppress excessive or generalized fear responses.
JCI Abstract Prefrontal correlates of fear generalization during endocannabinoid depletion Maladaptive fear generalization is one of the hallmarks of trauma-related disorders.
Here we show that 2-AG levels are inversely associated with fear generalization at the behavioral level in both mice and humans.
In mice, 2-AG depletion increases the proportion of neurons, and the similarity between neuronal representations, of threat-predictive and neutral stimuli within prelimbic prefrontal cortex neuronal ensembles.
In humans, increased dorsolateral prefrontal cortical-amygdala resting state connectivity is inversely correlated with fear generalization.
According to a recent study, 2-AG, a naturally occurring cannabinoid in the body, is essential for controlling fear reactions, especially in people who suffer from anxiety and PTSD. Lower 2-AG levels were found to be associated with heightened or overgeneralized fear responses to non-threatening stimuli in both humans and mice.
This shows that 2-AG functions as a natural filter for fear by assisting the brain in differentiating between threatening and benign stimuli. Scientists think it might be possible to create new, more potent treatments for anxiety-related disorders by focusing on this endocannabinoid system.
Key Facts:.
Fear Filter: The endocannabinoid 2-AG aids in reducing overreactions to fear.
Cross-Species Link: In both mice and humans, lower 2-AG levels were linked to increased fear.
Therapeutic Target: 2-AG might be a good target for novel therapies for PTSD and anxiety.
The Northwestern University is the source.
An investigation led by Northwestern Medicine and published in the Journal of Clinical Investigation suggests that certain cannabinoids made by the human body may help reduce excessive fear responses in individuals with anxiety and post-traumatic stress disorder.
“Inappropriate fear responses to stimuli that may or may not be similar to those experienced during their original trauma are common in people with anxiety and post-traumatic stress disorder (PTSD),” said Luis Rosas-Vidal, MD, PhD, assistant professor of Psychiatry and Behavioral Sciences and the study’s author.
Rosas-Vidal stated, “Your body’s endocannabinoid system controls the release of neurotransmitters by activating the same receptors as marijuana.”.
In particular, 2-AG, the compound of interest, has been linked to the regulation of anxiety and fear reactions. “”.
It was previously unknown, though, whether and precisely how the cannabinoid 2-AG (2-arachidonoylglycerol) works at the neuronal level to filter fear responses when exposed to novel stimuli, according to Rosas-Vidal.
In the study, researchers looked at how mice with low 2-AG levels responded to fear. They discovered that mice with 2-AG inhibition showed more fear reactions.
Using fiber photometry techniques, researchers discovered that lower endocannabinoid activity in the brain was linked to higher fear generalization.
“We discovered that inhibiting the endocannabinoid 2-AG essentially causes their fear reactions to become overly generalized,” Rosas-Vidal, who is also affiliated with the Stephen M. Stahl Center for Psychiatric Neuroscience, said.
Psychiatry and Behavioral Sciences Professor Lizzie Gilman and chair Sachin Patel, MD, PhD, was the study’s senior author.
Together with researchers from Linköping University and the University of Calgary, the researchers examined the relationship between 2-AG blood levels and fear generalization in human study subjects. Likewise, they discovered that greater fear generalization was linked to lower 2-AG levels.
Rosas-Vidal stated that the results collectively demonstrate the critical function endocannabinoids play in controlling fear reactions and point to 2-AG as a possible target for anxiety treatments.
He declared, “We believe our findings are really exciting.”. They demonstrate the behavioral and mechanistic mechanisms by which 2-AG controls fear reactions. “”.
Rosas-Vidal stated that he and his colleagues will keep researching the mechanisms underlying generalization as well as cannabinoid signaling in various neuron subtypes.
He stated, “We think these kinds of studies are very important in psychiatry to give us understanding of how psychiatric disorders arise and also point to potential treatments in the future.”.
Funding: The National Institute of Mental Health awarded grants K08MH126166 and R01MH107435 to support this study. Young Investigator Grant 29255 from the Brain and Behavior Research Foundation contributed additional funds.
Regarding this research news on PTSD and neuroscience.
Dimmer, Olivia.
Northwestern University is cited.
Get in touch with Olivia Dimmer at Northwestern University.
Picture: The picture is from Neuroscience News.
Original Study: Publicly available.
The study “Prefrontal correlates of fear generalization during endocannabinoid depletion” was written by Luis Rosas-Vidal and colleagues. JCI.
Abstract.
Fear generalization’s prefrontal correlates during endocannabinoid depletion.
One of the defining characteristics of trauma-related disorders is maladaptive fear generalization. It is unknown how the endocannabinoid 2-arachidonoylglycerol (2-AG) balances fear discrimination versus generalization, but it is essential for regulating anxiety, fear, and stress adaptation.
In order to tackle this issue, we combined neuroimaging and plasma endocannabinoid measurement from a mixed population of children who had been exposed to and not exposed to maltreatment with human and rodent fear conditioning models.
Here, we demonstrate that fear generalization at the behavioral level in both humans and mice is inversely correlated with 2-AG levels.
In the prelimbic prefrontal cortex of mice, 2-AG depletion increases the percentage of neurons that represent neutral and threat-predictive stimuli, as well as the similarity between neuronal representations. Fear generalization is inversely connected with greater dorsolateral prefrontal cortical-amygdala resting state connectivity in humans.
These findings support the idea that 2-AG deficiency may be a trauma-related disorder susceptibility endophenotype and offer convergent cross-species evidence that 2-AG is a crucial regulator of fear generalization.
