Enhanced excitatory synaptic transmission onto glutamatergic neurons in the basolateral amygdala may drive aging-related elevation in innate anxiety-like behaviors in male mice.

Anxiety disorders are the most common mental disorders in both young and old adults. However, most currently existing treatments, which are tailored for young patients, are not as effective in old patients. Therefore, investigating geriatric anxiety disorders would greatly benefit the mental wellbeing of the rapidly growing aged population. This study finds that innate anxiety-like behaviors elevate with aging in male mice. This study further identifies an aging-related increase in the excitatory synaptic transmission onto the glutamatergic neurons in the basolateral amygdala (BLA), which is mirrored by an increase in the expression of c-Fos, a marker of neuronal activity. Lastly, this study, by using chemogenetic intervention of BLA glutamatergic neurons, establishes a causal relationship between the aging-related increase in their neuronal activity and the aging-related elevation in innate anxiety-like behaviors in mice. Accordingly, we conclude that the aging-related microscopic physiological changes in BLA glutamatergic neurons might serve as a biological substrate underlying the aging-related elevation in innate anxiety-like behaviors. Thus, this study provides a potential intervention strategy for treating geriatric anxiety disorders, which is an urgent task given that the available treatments do not meet actual needs, while the affected population is rapidly growing.