In a study published in Nature Communications, researchers from Dr. XU Xiaohong’s lab at the Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences, delineated a circuit that was essential for anxiety-like behavioral avoidance. 

Anxiety represents an emotional state of apprehension about potential or unpredictable threats. Previous studies found that many species, including fish, rodents, and primates, showed increased anxiety levels after predator encounters, and anti-anxiety drug treatment reduces the avoidance of predator cues in normal animals. These results indicated that anxiety may be an emotion evolutionarily rooted in predator defense. However, whether brain areas regulating predator defense also regulate anxiety-related behaviors remained poorly understood.   

To answer this question, Dr. XU’s lab focused on the anterior hypothalamus (AHN), a node of the hypothalamus defensive system.  

They first found that an unfamiliar object introduced in the center of an open field could elicit a more robust avoidance of the center and preference for the periphery in mice, suggesting elevated anxiety levels. In vivo calcium recording showed that the neural activity of AHN GABAergic (AHN^Vgat+) neurons ramped as mice approached the unfamiliar object. Moreover, the single-unit recording showed overlapping AHN neural ensembles activated during object approach and fox urine exposure.  

Next, AHN^Vgat+ neuron activity was much higher in open arms than in closed arms of an elevated plus maze (EPM). Interestingly, the AHN^Vgat+ neuron activity positively correlated with anxiety-like avoidance behaviors induced by the object and by the EPM open arm, while acute optogenetic inhibition of AHN^Vgat+ neuron activity could diminish anxiety-like avoidance behavior in both paradigms.  

To explore the upstream brain region that transmits the anxiety-like information to AHN, the researchers combined virus tracing and circuit dissection study, and found vSub as the main upstream area that sent monosynaptic excitatory inputs to AHN to modulate anxiety-like avoidance behavior.  

These results uncovered a circuit from vSub to AHN necessary for anxiety-like avoidance behavior, revealing that AHN is the site of convergence between predator defense and anxiety-related behaviors.