Scientists Discover 'Anxiety' Neuron Cells in Mouse Brains

Nobody wants to be told that their mental health issues are all in their head. But what if that was literally true? If scientists could point to the part of the brain that’s responsible for exaggerated responses or dysfunctional thinking, it might be comforting, like finally diagnosing the cause of an illness. In recent years, scientists have gained a greater understanding of the anatomical roots of mental illness, and now, a team of neuroscientists has pinpointed a group of cells involved in anxiety responses.

In a paper published Wednesday in the journal Neuron, researchers at Columbia University Irving Medical Center and the University of California, San Francisco captured live footage of cells in the hippocampus — the region of the brain associated with emotion and memory — of mice that fire when the animal is experiencing anxiety. The discovery could lead scientists to identify more precise targets for anxiety therapy in humans because we are likely to have an equivalent group of cells in our own brains.

For the nearly 20 percent of adults who live with anxiety in the United States, better therapies could make daily life more comfortable and less, well, anxious.

To conduct the new study, the researchers inserted tiny microscopes into mouse brains and put the mice in a maze. This maze contained several pathways, some of them closed and some of them open. Mice, typically burrow- or hole-dwellers, are anxious in open spaces, possibly because that’s where they are most exposed to predators. Accordingly, when the mice reached the portions of the maze that led into open space, their anxiety registered as neurons firing in the hippocampus.

Then, the researchers fiddled with these neurons, increasing and decreasing their activity. Just as suspected, when these anxiety neurons fired more, the mice were so anxious that they’d barely explore. When the neurons were inhibited, however, the open spaces didn’t trigger a fear response.

The researchers say this could open doors for new therapeutic approaches, potentially ones that won’t have as many off-target effects as typical anxiety medications, like benzodiazepines.

Abstract: The hippocampus is traditionally thought to transmit contextual information to limbic structures where it acquires valence. Using freely moving calcium imaging and optogenetics, we show that while the dorsalCA1 subregion of the hippocampus is enriched in place cells, ventral CA1 (vCA1) is enriched in anxiety cells that are activated by anxiogenic environments and required for avoidance behavior. Imaging cells defined by their projection target revealed that anxiety cells were enriched in the vCA1 population projecting to the lateral hypothalamic area (LHA) but not to the basal amygdala (BA). Consistent with this selectivity, optogenetic activation of vCA1 terminals in LHA but not BA increased anxiety and avoidance, while activation of terminals in BA but not LHAimpaired contextual fear memory. Thus, the hippocampus encodes not only neutral but also valence-related contextual information, and the vCA1-LHApathway is a direct route by which the hippocampus can influence innate anxiety behavior.