We aim to uncover the neural mechanisms underlying the homeostatic regulation of appetite and cardiometabolic physiology. To do so, we use genetically engineered mouse models and Cre-dependent AAVs to specifically map neuronal circuits as well as manipulate and record their activity in order to define function. Making this possible are a variety of modern neuroscience tools including chemogenetics, channelrhodopsins, genetically encoded calcium indicators, and modified G-deleted rabies viruses for behavioral, hormonal, electrophysiological, and anatomical circuit mapping studies. Recently, we have applied these methodologies to investigate adrenal steroid hormone influences on appetite by defining a role for hindbrain aldosterone-sensing neurons in sodium appetite and demonstrating that glucocorticoids stimulate hunger through direct activation of hypothalamic AgRP neurons. In addition, we are interested in the discovery of previously unidentified, genetically defined neuronal subtypes within the hypothalamus and brainstem that regulate energy and fluid balance. To achieve this, we use single-cell RNA sequencing and bioinformatics to classify transcriptionally unique neuronal populations in an unbiased manner. Subsequently, we use CRISPR/Cas9 technology to engineer new Cre knockin mouse lines in order to gain specific access to these neuronal subtypes for functional characterization studies. Our combined use of next generation sequencing, transgenic mouse engineering, physiology, and behavior is well suited for mechanistic investigation of neural circuits regulating appetite, metabolism, and endocrine function.