Tucked away in the temporal lobe, near the base of our brains, is a small, almond-shaped area called the amygdala, which processes our emotions. Neuroscientists at Tufts University have examined the symphony of signals created in a subsection of this area — the basolateral amygdala — to better understand how they contribute to negative feelings such as fear and anxiety.
This emotional processing hub plays a role in many different behaviors. We are interested in how the network switches to these negative states, which are relevant for many different conditions, such as depression and post-traumatic stress disorder.†
Jamie Maguire, a Kenneth and JoAnn G. Wellner Professor, Neuroscience Department, Medical Faculty, Tufts University
Maguire is a member of the Faculty of Neuroscience of the Graduate School of Biomedical Sciences (GSBS).
In a recent article published in the journal eNeuro, Maguire and her colleagues found that alcohol can alter the activity pattern in the basolateral amygdala in a mouse model, essentially allowing the brain’s orchestra to play a different tune. This is the first study to show that alcohol is able to alter these patterns, known as network states. Their work opens the door to a better understanding of how the brain switches between different activity patterns related to anxiety or other moods, which may also be relevant to alcohol dependence.
“We know that one of the reasons people drink is to relieve anxiety or stress, which are related to this part of the brain,” said Alyssa DiLeo, the paper’s lead author and a GSBS doctoral student in the lab at the time. maguire. of the study. “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 a mouse’s brain into a less anxious state and into a more relaxed state. They were also able to identify specific receptors in the basolateral amygdala, known as delta subunit-containing GABA-A receptors, 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 seemed to need more alcohol than males to change their network status, which may be related to the fact that female mice have fewer of the relevant receptors. In addition, when the researchers removed these receptors in male mice, the altered mice responded like their female counterparts.
“That tells us that these receptors play a role in these sex differences and how alcohol affects the basolateral amygdala network,” Maguire said.
An anxious state of mind
Earlier this year, Maguire and her team collaborated with cell and molecular biology professor Jeffrey Tasker of Tulane University and other researchers to locate another set of receptors in the basolateral amygdala that appear to be relevant to an animal’s fear response. In a study published in nature communicationthe researchers used noradrenaline, a hormone similar to adrenaline, to stimulate the basolateral amygdala in mice and put them in a fearful state.
Norepinephrine can interact with several neural receptors, but when the researchers turned off one, specifically the 1A adrenoreceptor, the animals’ brains stopped going into fearful mode.
“If you block norepinephrine’s ability to communicate with cells through this receptor, you lose norepinephrine’s ability to create a state of fear,” said Eric Teboul, a GSBS doctoral candidate in Maguire’s lab and lead author of the paper. . “Being able to create a binary behavior — anxious or not anxious — gives us insight into how the brain actually calculates and does things.”
By understanding the molecular interactions that switch the basolateral amygdala in and out of these negative network states, the researchers can find potential drug targets to help people treat mood disorders and addiction. For example, a person suffering from post-traumatic stress disorder may be stuck in an anxious pattern of neural activity. By breaking that pattern, they can recover.
Of course, it won’t be as simple as turning these circuits on or off, Teboul said.
“You don’t just want to take away the fear; you don’t want to take away the sadness; you don’t want to take away the stress because there are good reasons why we feel stressed and afraid of things,” he said. “We want to understand how this amygdala region calculates things so that we can balance it at a normal level.”
DiLeo, A., et al† (2022) Sex differences in the alcohol-mediated modulation of BLA network states. eNeuro† doi.org/10.1523/ENEURO.0010-22.2022