The brain and the immune system form a bi-directional communication system so that each regulates the function of the other. We have a growing interest in how products of the immune system, such as the pro-inflammatory cytokines, regulate central nervous system function and the implications of this immune-to-brain loop for mood, cognition, and pain. That is, we are interested in the sensory functions of the immune system by which it informs the brain that a pathogen is in the periphery. Projects focus on: 1) How the cytokine signal reaches the brain to alter neural activity. The major theme is that cytokines can activate peripheral afferent nerves such as the vagus, thereby generating neural input to the brain as well as blood-borne input, 2) The generation of cytokines within the brain in response to signaling from the immune system and the role of these cytokines in mediating host defense, 3) The impact of immune-to-brain signaling and brain cytokine production on anxiety and depression, the idea being that these are sufficient causes of anxiety and/or depression, 4) The impact of immune-to-brain signaling and brain cytokine production on learning and memory, the basic finding being that these processes disrupt memory formation that requires the intact functioning of the hippocampus, and 5) Pain.