EARLY LIFE STRESS ALTERS AMYGDALA DEVELOPMENT IN A SEX-SPECIFIC MANNER

It is well established that early life stress (ELS) drastically affects the developing brain, in particular impacting the limbic system. However, the finer details of its effect on the microcircuit development, such as compensatory processes and changes in excitation/inhibition balance of the network, remain to be elucidated.
Aims: To explore and compare the immediate and the long-term effects of ELS on the circuitry of the lateral amygdala in a mouse model.
Methods: To induce ELS we used a limited bedding and nesting model with WT, PV- and Sst-Cre mice with subsequent behavioural validation. Electrophysiological recordings were performed in the lateral amygdala in acute slices at P18-21 and P60-P80.
Results: At juvenile age, we observed an increase in glutamatergic inputs to Sst and PV interneurons and a reduction of their excitability in both male and female mice. However, by adulthood, these changes turned to the opposite in males while effectively recovering in females. Even though female mice displayed amygdala hyperexcitability early on, they recovered from these perturbations in adulthood, while males developed an anxiety phenotype associated with principal cell hyperexcitability.
Conclusions: Even though the changes immediately following ELS were similar between male and female animals, only the male mice developed an anxiety phenotype in adulthood. Our data support that this male-specific ELS-induced pathology is driven by reduced excitatory inputs to amygdala interneurons, which contribute to the hyperexcitability of principal cells. Furthermore, ELS males displayed precocious network development, demonstrating the excitation/inhibition ratio characteristic of adult animals already by P21.