c-fos Expression as a Marker of Functional Activity in the Brain: Immunohistochemistry

Neuroscientists are often faced with the choice of obtaining quantitative data at the expense of morphological information or vice versa. The identification of a pathway in the brain offers a potential anatomical basis for a given physiological function, for example, but does not directly address the physiological significance of the pathway. Conversely, measurements made from tissue homogenates provide clues to the response of cells to a stimulus but cannot tell us anything about the specific cells in which changes occur. This chapter describes an approach that bridges the gap between morphological data and physiological significance. The presence of Fos, the protein product of the immediate-early gene c-fos, in a neuron has become a popular means to identify neurons that participate in a given function without losing the ability to know precisely where these neurons are. A brief description of the techniques that were supplanted by Fos immunohistochemistry will be followed by a discussion of c-fos and why its expression as a marker of functional activity has gained such popularity in the neurosciences. Techniques for Fos immunohistochemistry, their compatibility with other techniques, and important considerations regarding analyses of data obtained with these approaches will be presented.