Progress in the study of the mechanism of new circuits of anxiety-like behavior in mice

On December 3, 2022, Nature Communications published online the research group of Xu Xiaohong, a researcher at the Center for Excellence in Brain Science and Intelligent Technology (Institute of Neuroscience) and State Key Laboratory of Neuroscience, Chinese Academy of Sciences, entitled "A circuit from the ventral subiculum to anterior hypothalamic nucleus.
" GABAergic neurons essential for anxiety-like behavioral avoidance"
.
The study analyzed the role of neural circuits from ventral subiculum (vSub) to anterior hypothalamus (AHN) from ventral hypothalamus (AHN) in regulating anxiety-like avoidance behavior in mice through techniques such as bulk calcium signal recording, single-channel recording, optogenetics, and patch-clamp techniques
.

Anxiety is an emotional state
that arises in the face of a potential or unclear threat.
Previous studies have found that many species, including fish, rodents and primates, experience increased anxiety levels after encountering predators, and that the use of anxiolytic drugs can reduce avoidance behavior in response to predator signals
.
These phenomena suggest that anxiety may be evolutionarily related to predator defenses, and it is unclear
whether nuclei, which are involved in predator defenses, are also involved in regulating anxiety behavior.

In response to this problem, the research team carried out research
on the AHN nuclear group.
AHN tradition is considered a link
in the hypothalamic defense system.
The researchers found that when unfamiliar objects were placed in the center of the open field, the attachment of mice and the avoidance of the center area of the open field were significantly enhanced, indicating an increase
in anxiety levels.
By recording calcium signals in vivo, the researchers found that the neural activity of AHN's GABAergic neurons (AHN^Vgat+) gradually increased as mice approached objects (Figure 1).

By recording in vivo single-channel, the researchers found that the same neuron of AHN can respond to both unfamiliar objects and fox urine, which represents signals from natural enemies
.
On another behavioral paradigm that tests anxiety-like behavior, elevated plus maze (EPM), the team also found that the activity of AHN^Vgat+ neurons on the open arm of EPM was significantly higher than that on the closed arm of EPM through the recording of body calcium signals
.
Using correlation analysis, it was found that signals from AHN^Vgat+ neurons approaching objects and rising on EPM open arms predicted avoidance behavior
in mice.
After inhibiting the neural activity of AHN^Vgat+ neurons by optogenetic inhibition, the anxious-like avoidance behavior caused by unfamiliar objects and EPM open arms in mice was significantly reduced
.
Using viral tracer and loop studies, vSub delivered anxiety-related information to AHN and regulated anxiety-like avoidance behavior
in mice.
The study shows that AHN can process both information related to natural enemy stimuli and anxiety-related information, revealing the function of neural circuits from vSub to AHN in anxiety-like avoidance behavior in mice, and deepening the understanding
of the neural mechanism of anxiety.

The research work has been supported
by the Ministry of Science and Technology, the Chinese Academy of Sciences, the National Natural Science Foundation of China, and the Shanghai Municipal Science and Technology Commission.

Source: Center for Excellence in Brain Science and Intelligent Technology, Chinese Academy of Sciences

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