Even though ketamine has been heralded as a significant advance in the development of novel and rapidtreatments for depression, the acute psychotomimetic and reinforcing effects of this drug limit its utility.Previously, we demonstrated that activation of a circuit from the ventral hippocampus to the medial prefrontalcortex is both necessary and sufficient for ketamine?s sustained antidepressant-like effects in rats.

Even though ketamine has been heralded as a significant advance in the development of novel and rapidtreatments for depression, the acute psychotomimetic and reinforcing effects of this drug limit its utility.Previously, we demonstrated that activation of a circuit from the ventral hippocampus to the medial prefrontalcortex is both necessary and sufficient for ketamine?s sustained antidepressant-like effects in rats.

The hypothalamus is the brain hub that regulates energy homeostasis. The genetic and molecular basis of thisregulation in humans is not well understood as access to this tissue is a major barrier and available onlypostmortem. To overcome the barrier of limited tissue access, we are generating induced pluripotent stem cell(iPSC)-derived neuronal cultures that recapitulate many of the features of hypothalamic neurons from thearcuate nucleus, including by benchmarking this in vitro model to in vivo events that are pivotal in hypothalamicdevelopment.