Discovery of "anxiety cells" in mice could lead to better therapies
Anxiety is an important emotional state, having evolved to help us be on guard in the face of potential threats. But in the modern world anxiety manifests in a multitude of dysfunctional ways, leaving many people suffering from debilitating disorders. A new study has opened up a potential pathway to future anti-anxiety treatments after effectively demonstrating the identification of specific "anxiety cells" in the brains of mice and successfully turning those cells on or off with beams of light.
Past research has indicated that the hippocampus is fundamental to how the brain processes feelings of anxiety. It's known that the hippocampus actively communicates with the amygdala and the hypothalamus, areas of the brain that control heart rate, stress hormones and other anxiety-related behaviors.
This new study from neuroscientists at UC San Francisco and the Columbia University Irving Medical Center set out to try to home in on which specific cells in the hippocampus could be orchestrating these feelings of anxiety. Using a method called calcium imaging, which allows for the identification of neuronal cells as they become active, the researchers were able to watch individual cells in the ventral region of the hippocampus activating as mice were provoked by anxiety-inducing scenarios.
"We call these anxiety cells because they only fire when the animals are in places that are innately frightening to them," says Rene Hen, a senior investigator on the study. "For a mouse, that's an open area where they're more exposed to predators, or an elevated platform."
Not only did the activity of the very specific cell clusters correspond with the anxiety levels observed in the mice, but the output of those activated hippocampus cells were seen to directly point toward the hypothalamus.
The researchers then used a technique called optogenetics, in which light is used to control genetically-defined neurons, to switch those anxiety cells either on or off. And the results were immediately clear. Activating those ventral hippocampus cells increased anxiety and avoidance behaviors, even when the animals were in "safe" spaces. Conversely, silencing those same cells resulted in an impairment of fear-modulated behavior, so the mice wandered more consistently into open spaces or onto elevated platforms.
Of course, anxiety is a great deal more complex than the activation of just a few cells in the hippocampus, but this research could ultimately have positive and practical outcomes in helping find targets to modulate extreme anxiety-based behaviors in some people. The next step for the researchers is to study these "anxiety cells" in greater detail and try to find out if they function similarly in humans.
"We're looking to see if these cells are different molecularly from other neurons," Hen said. "If there's a specific receptor on the cells that distinguishes them from their neighbors, it may be possible to produce a new drug to reduce anxiety."
The research was published in the journal Neuron.