The study determines how the emotional center of the brain contributes to negative feelings

In the temporal lobe, near the base of our brain, is a small almond-shaped area called the amygdala, which processes our emotions. Tufts University neuroscientists have examined the symphony of signals generated in a subsection of this region—the basolateral amygdala—to better understand how they contribute to negative feelings such as anxiety and fear.

This emotional processing center plays a role in many different behaviors. We are interested in how the network switches to these negative states, which is relevant to many different disorders such as depression and post-traumatic stress disorder..”

Jamie Maguire, Kenneth and JoAnn G. Wellner Professor, Department of Neuroscience, Faculty of Medicine, Tufts University

Maguire is a faculty member of the Neuroscience Program at the Graduate School of Biomedical Sciences (GSBS).

In a recent article published in the journal eNeuroMaguire and her colleagues found that alcohol can change the pattern of activity in the basolateral amygdala in a mouse model, essentially telling the brain’s orchestra to play a different tune. This is the first study to show that alcohol is able to alter these patterns, often referred to as network states. Their work opens the door to a better understanding of how the brain switches between different activities associated with anxiety or other moods, which may also be relevant to alcohol addiction.

“We know that one of the reasons people drink is to relieve anxiety or stress, which is associated with this area of ​​the brain,” said Alyssa DiLeo, who is the first author of the paper and was a GSBS postdoctoral fellow in Maguire’s lab at the time. studies. “Discovering how alcohol changes these network states may be the first step in understanding the transition from first drink to alcohol use disorder.”

The researchers found that alcohol can essentially shift the mouse brain into a less anxious and more relaxed state. They were also able to identify specific receptors in the basolateral amygdala, known as GABA-A receptors containing the delta subunit, as an important part of the signaling network that causes this switch.

The effects were slightly different in male and female mice, Maguire said. Females appeared to need more alcohol than males to change the state of the network, which may be related to the fact that female mice have fewer relevant receptors. Additionally, when the researchers removed these receptors in male mice, the altered mice responded like their female counterparts.

“This tells us that these receptors play a role in these gender differences and how alcohol affects the basolateral network of the amygdala,” Maguire said.

Terrible state of mind

Earlier this year, Maguire and her team teamed up with Tulane University cell and molecular biology professor Jeffrey Tasker and other researchers to identify a different set of receptors in the basolateral amygdala that appear to be relevant to the animal’s fear response. In a study published in The nature of communicationThe researchers used norepinephrine, a hormone similar to adrenaline, to stimulate the basolateral amygdala in mice and switch them into a fearful state.

Norepinephrine can interact with several nerve receptors, but when the researchers deactivated one in particular, the α1A adrenoreceptor, the animals’ brains no longer went into fear mode.

“If you block the ability of norepinephrine to communicate with cells through this receptor, then you lose the ability of norepinephrine to create a fear state,” said Eric Teboul, a GSBS doctoral student in Maguire’s lab and lead author of the paper. “Being able to create a binary behavior—fear or fear—gives us insight into how the brain actually computes and does things.”

By understanding the molecular interactions that switch the basolateral amygdala in and out of these negative network states, researchers can find potential drug targets to help treat mood disorders and addiction in humans. For example, a person suffering from post-traumatic stress disorder may become stuck in a terrible pattern of neural activity. Disrupting this pattern could help them recover.

Of course, it won’t be as simple as turning these circuits on or off, Teboul said.

“You don’t want to get rid of fear; you don’t want to get rid of sadness; you don’t want to get rid of stress, because there are good reasons why we feel stressed and afraid of things.” he said. “We want to understand how this area of ​​the amygdala calculates things so we can balance it to a normal level.”