The ability of animals to mount adaptive responses to emotional and physiological stress is mediated by central neural pathways that control neuroendocrine secretion, autonomic function, and motivated behavior. The long-term objective of research in the Rinaman lab is to characterize the functional multisynaptic organization of these neural systems, with a focus on circuits that relay visceral sensory (interoceptive) feedback to the brainstem, hypothalamus, and limbic forebrain. Neuroanatomical, physiological, and behavioral techniques are applied to probe these circuits in transgenic and wildtype laboratory rodents, offering unique opportunities to test hypotheses about brain structure-function relationships. Currently funded projects focus on central noradrenergic and glucagon-like peptide 1 (GLP1) neural signaling pathways arising from caudal brainstem. Some ongoing studies analyze stimulus-induced expression of the immediate-early protooncogene c-fos (a marker of neural activation) after animals are exposed to various stress- and anxiety-provoking challenges. Analysis of c-fos expression is combined with retrograde labeling of central neural pathways and immunocytochemical or in situ hybridization (RNAscope)-based detection of neurotransmitter chemicals or mRNA to characterize the axonal projections and phenotypes of stimulus-activated neurons. Other projects use adeno-associated viral (AAV) vectors and engineered neurotropic alpha herpes viruses for condtional transneuronal tracing of multisynaptic neural circuits. Transgenic cre-driver mice and rats also are used for conditional viral-based manipulation of neural activity using DREADDs and optogenetics. Sophisticated microscopic approaches (including CLARITY-based confocal and lightsheet microscopy) enable high-level visualization and mapping of anatomical circuits.