The use of c-fos as a metabolic marker in neuronal pathway tracing

The use of c-fos protein (Fos) immunocytochemistry as a metabolic marker for tracing neuroanatomical connections, seizure pathways and sites of action of neuroactive drugs is discussed in this report. Fos immunocytochemistry will be very useful for these purposes providing that a number of potential problems are recognized and controlled. These include the observations that Fos exists basally in neurons and can be non-specifically elevated after behavioural stress; neuronal bursting is required to elevate Fos in neurons in anaesthetized animals; drugs such as ketamine can block Fos elevation in neurons; the time-course of Fos induction and decay varies with different inducing stimuli and the brain region sampled; and some brain regions do not express Fos after any treatments tried so far. To overcome these potential problems we list a number of steps that should be followed when using Fos immunocytochemistry as a metabolic marker of brain activity.