Fear response neurons identified as potential anxiety treatment target
Researchers at the University of North Carolina (UNC) School of Medicine have discovered a set of neurons in the mouse brain that appear to control physiological responses to fear, like heart palpitations and pupil dilations. Tests in mice suggest that this region could be a new drug target for anxiety treatments.
Anxiety plays an important evolutionary role, activating the fight-or-flight response in the face of imminent danger. But for us modern humans, who generally don't need to be on constant alert for tigers, the feeling often manifests itself as an array of anxiety disorders, where unpleasant biological responses arise disproportionately to fear triggers, or linger for weeks, months or even years.
Finding ways to dampen this overactivity could help people with these conditions, but it’s a challenge to untangle all the different areas of the brain to figure out what does what. Now the UNC researchers have zoomed in on one particular area that appears to play a vital role.
Inside the amygdala is the bed nucleus of the stria terminalis (BNST), a small region previously found to be responsible for physiological fear responses. Within the BNST, the researchers zoomed in even further to a set of neurons that express a neurotransmitter gene called Pnoc.
Pnoc has previously been linked to pain sensitivity and motivation, and in the new study the team imaged the neurons that express it. Using two-photon microscopy, the researchers observed the activity of Pnoc neurons in mice while the animals were being exposed to either pleasant or unpleasant odors.
The team observed that in response to both smells, these neurons would fire and the pupils of the mice would quickly dilate – which can be either an anxiety and reward reaction, depending on the situation.
In the next experiments the researchers took a more active approach. They used optogenetics, a technique where laser light is used to either activate or silence specific cells – in this case, the Pnoc neurons. Then they measured the physical responses of the mice. Sure enough, activating Pnoc neurons caused the animals’ pupils to dilate and their heart rates to increase.
Next, the mice were made to navigate a maze set up to induce anxiety. When the animals’ neurons were optogenetically activated, their signs of anxiety increased, while using the method to quiet them reduced those signs.
“Essentially we found that activating these BNST Pnoc neurons drives arousal responses and worsens anxiety-like states,” says Jose Rodríguez-Romaguera, first author of the study.
The team says that the findings suggest that the Pnoc neurons in the human brain could be a potential new target for future anxiety drugs, helping to reduce unpleasant or excessive physical responses.
But of course, before this can ever be tested in humans, much more work needs to be done in animals. That includes identifying the subgroups of the Pnoc neurons, which all seem to have different responses to positive or negative stimuli.
The research was published in the journal Cell Reports.
Source: UNC School of Medicine