“A circuit from the ventral subiculum to anterior hypothalamic nucleus GABAergic neurons essential for anxiety-like behavioral avoidance” was published in Nature Communications on December 3, 2022. This study was performed by researchers in Dr. XU Xiaohong’s Lab at the Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences.   

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. Moreover, anti-anxiety drug treatment reduces the avoidance of predator cues in normal animals. These results indicate 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 Xiaohong’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 (Figure 1). In vivo calcium recording further found 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.  

Furthermore, AHN^Vgat+ neuron activity was much higher in open arms than in closed arms of an elevated plus maze (EPM). Moreover, 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, they combined virus tracing and circuit dissection study. They found vSub as the main upstream area that sent monosynaptic excitatory inputs to AHN to modulate anxiety-like avoidance behavior.  

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

The research was completed by YAN Jingjing, under the supervision of Dr. XU Xiaohong, with the help from DING Xiaojing, CHEN Aixiao, ZHANG Wen, YU Zixian,Dr. LI Haohong’s lab (HE Ting, HE Mengge), Dr. CAO Peng’s lab (CHENG Xinyu, XIE Zhiyong) and Dr. XU Chun’s lab (WEI Chuanyao) . This work was supported by the Ministry of Science and Technology of China, Chinese Academy of Sciences, the National Nature Science Foundation of China,and Shanghai Municipal Science and Technology Commission. 

　AUTHOR CONTACT: 

　XU Xiaohong 

　Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences, China.  

　E-mail: xiaohong.xu@ion.ac.cn