Systems & Behavioral Neuroscience @ UVa

Sensing the immune system: how the brain detects and processes signals from the immune system...

How do we know we are sick? When we are infected, specialized immune cells signal our brains to start a fever, make us feel miserable and cause all the other familiar symptoms of sickness, such as fatigue and the inability to concentrate on tomorrow’s exam. Work in the Goehler lab is focused on determining the exact ways through which the immune system signals the brain. The immune system functions as a sensory system tuned to detect chemical constituents of dangerous micro-organisms, and to alert sensory components of the peripheral and central nervous systems.We are analyzing this immunosensory system as a whole in the same way that other sensory systems are studied: by investigating such issues as signal transduction, receptive field characteristics, and neural pathways in the brain driven by infection. We use a combination of behavioral, pharmacological, surgical and many anatomical techniques. The latter include immunocytochemistry and neuronal tract-tracing.Our lab also studies how immune system-derived signals contribute to shifts in affective states, especially anxiety. We aim at elucidating the neurocircuitry that contributes to infection and immune activation-related anxiety by assessing neural activation that correlates with behavioral measures of anxiety in response to food-borne infectious bacteria or bacterial products.

Our current work and findings

	Neurons and Immune Cells: A section through the area postrema in the lower brain stem. This is a structure in the lower brain stem that lacks the blood brain barrier and thus can sense blood components directly. Within this structure, many immune cells labeled by their MHC class II receptors (stained black) intermingle with neurons stained orange-brown for the dopamine-synthesizing enzyme tyrosine hydroxylase.
	Neurons activated by immune stimulants: This image shows a part of the brain (the nucleus of the solitary tract) containing neurons that are activated by a bacterial immune stimulant. Activated nerve cells can be recognized by their dark back cell nucleus (see black arrows) appearing as little black beads. This black staining locates the c-fos protein, an activation marker that is not expressed in "quiet" neurons. The orange-brown staining marks the presence of tyrosine hydroxylase, a marker for catecholaminergic neurons. Some of these neurons show both black and brown markers together, showing particular catecholaminergic neurons responsive to abdominal immune stimulation.
	Close up immune cells: This image shows a close up of an immune cell with arborizing processes (black) in close apposition with neurons (brown) that are located within the area postrema.
	Sensory ganglia activated: This image shows a part of the vagal sensory ganglion located in the neck that contains the nerve cell bodies of nerve fibers that extend all the way into the thorax and abdomen, and their axons into the brain stem. Some of these cell bodies show a granular reaction product indicative of the expression of messenger RNA encoding the activation marker c-fos. This activation was induced by intraperitoneal injection of the bacterial immune stimulant SEB.