An amygdala to anterior hypothalamic circuit gates stress sensitivity

Key Points:

• The study used C57BL/6J mice, both male and female, aged 2–6 months, with no observed sex differences in behavior or neuronal recordings, and all procedures were approved by the Icahn School of Medicine IACUC.
• Various surgical procedures were performed including viral infusions for calcium imaging, optogenetics, and chemogenetics targeting specific brain regions like the AHN and BLA, followed by implantation of GRIN lenses or optic fibers for neural recording and manipulation.
• Behavioral testing involved stressor exposures (footshock and auditory stimuli) in distinct contexts, habituation protocols, and assays such as the light–dark test, with freezing and motion quantified using specialized software; optogenetic and chemogenetic manipulations were applied during these tests.
• Whole-brain c-Fos immunostaining and iDISCO clearing were used to map neuronal activation, with light-sheet microscopy and custom image analysis pipelines aligning data to the Allen Brain Atlas for regional quantification and correlation analyses.
• Calcium imaging data were processed with motion correction and CNMF algorithms to extract neuronal activity, and statistical analyses including negative binomial regression, hierarchical clustering, and ANOVA were performed using R, with all data and code publicly available.