Neuroanatomical tracing at high resolution

Most techniques used for the study of the fiber connectivity in the central nervous system produce results which are visualized in the conventional light microscope or fluorescence microscope. Although in some cases this may be sufficient, often proof is necessary that fibers which enter a particular brain area indeed terminate here. Alternatively, it may be necessary to determine whether the axon terminals of traced fibers form synapses with specific processes of specific neurons. With the latter neurons all cellular elements are meant which can be labeled in some way. Evidence of synaptic connectivity necessitates visualization at a higher level of resolution, that is at the electron-microscopic level. In this contribution to the Special Issue we discuss several methods currently available to visualize individual tracers, and methods developed to visualize two different markers, that is one marker attached to a fiber or an axon terminal, and the second marker attached to a presumed pre- or postsynaptic neuronal element.