Central role of regular firing neurons of centrolateral amygdala in affective behaviors.

Anxiety and depression are highly prevalent psychiatric disorders with poorly understood neural mechanisms. The amygdala, particularly its hyperactivity, is strongly implicated in anxiety. Mice overexpressing the gene display anxiety, depression, social deficits, and disrupted amygdala excitability, inducing output circuit imbalance. To dissect the role of specific amygdala neuron populations, we created mice with extra copies of and floxed native alleles. We normalized dosage selectively in the basolateral amygdala (BLA) pyramidal cells via stereotaxic injection of AAV-CRE-GFP, using AAV-GFP as a control. Electrophysiological recordings from centrolateral amygdala (CeL) revealed that the normalization of restored synaptic strength in regular but not late firing neurons. Behaviorally, this intervention reversed anxiety, depression, and social deficits, but not object recognition memory impairments. These results highlight the critical role of regular firing CeL neurons in affective disorders and suggest that targeting their activity may offer new strategies for treating anxiety and depression.