Amygdala GABA Neurons: Gatekeepers of Stress and Reproduction

Stress causes menstrual disturbances, infertility and other reproductive disorders. The posterodorsal medial amygdala (MePD) not only processes stress signals but is a critical modulator of the gonadotropin-releasing-hormone (GnRH) pulse generator, via GABAergic inhibitory projections to the hypothalamus. However, the mechanisms by which stress is processed within the MePD, particularly via the high density of GABAergic and Urocortin-3 (UCN3) neurons, remain poorly understood. Here, we combine in-vivo GRadient-INdex (GRIN) lens mini-endoscopic calcium imaging (proxy for neuronal activity) with optogenetics and computational modelling to elucidate the underlying circuitry and its dynamics. Our results reveal two anti-correlated GABAergic subpopulations in the MePD that dictate responses to both UCN3 neuron stimulation and restraint stress. Our computational model attributes the anti-correlated activity to mutually inhibitory interactions between the two GABAergic subpopulations and predicts how these interactions shape downstream-responses to stimulation of GABAergic and UCN3 neurons. We test these predictions using optogenetics and show that GABAergic neurons operate downstream of the UCN3 population, playing a critical role in relaying UCN3 signals to modulate LH pulse frequency. Our study demonstrates for the first time how GABAergic neurons in the amygdala regulate the effects of stress on reproductive functions, revealing key neural mechanisms that link emotional and reproductive health.