Enhanced excitatory synaptic transmission onto glutamatergic neurons in the basolateral amygdala may drive age-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 current treatments, which are tailored for young patients, are not as effective in old patients. Therefore, investigating geriatric anxiety disorders would greatly benefit the mental well-being of the rapidly growing aged population. This study finds that innate anxiety-like behaviors elevate with age in male mice. This study further identifies an age-related increase in excitatory synaptic transmission onto 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 on BLA glutamatergic neurons, establishes a causal relationship between the age-related increase in their neuronal activity and the age-related elevation in innate anxiety-like behaviors in mice. Accordingly, we conclude that the age-related microscopic physiological changes in BLA glutamatergic neurons might serve as a biological substrate underlying the age-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.