Neuroanatomical tract-tracing methods beyond 2000: what's now and next

Looking back at the great events that took place in the 20th century within the discipline of neuromorphol-ogy, it is evident that two periods of great acceleration can be distinguished, one at the very beginning and one at the end of this remarkable century. The first of these periods, the Golgi/Cajal re6olution, actually started in the last decade of the 19th century and it moved on at full speed during the first three decades of the next century. The initial discovery by Camillo Golgi and the intelligent exploitation by Santiago Ramon y Cajal and co-workers of what became known as the Golgi silver-impregnation technique, caused an enormous increase in the number of neuromorphological studies. The final outcome of these studies was the wide and final acceptance by the neuroscience community of the neuron doctrine. The second or tracing re6olution saw its birth during the late 1960s and accelerated to full momentum in the early 1970s. Like its Golgi/Cajal predecessor, this revolution was set in motion by technological innovation , notably the use of naturally occurring cellular transport for fiber tracing purposes. This second revolution has provided the solid neuroanatomical background for many concepts of brain function. Both periods of acceleration in the 20th century can thus be characterized as being 'technology-driven', and both resulted in a spectacular increase in understanding of the anatomy of the brain. When we concentrate on the second period of rapid progress, we note that an amazing array of tracing methods and tracers has been introduced, together with other innovations like immunocytochemistry and electron microscopy. Researchers are now facing a quickly changing scenario in which the boundaries between classical disciplines such as neuroanatomy, neurochem-istry, neurophysiology and neuropharmacology can no longer be maintained. Information becoming available from marriages between these fields of research is very impressive and therefore the available technical tools have to be adapted to fulfil the requirements inherent to the complex investigations involved. Although it may be too early, the end of the Decade of the Brain may be seen as a pivotal point. We are finding ourselves in a promising position from which we can look back at what has happened and enjoy the availability of a number of new and impressive techniques. Alternatively, we can look forward and conceive challenging research to further explore the anatomy of the brain and the complex circuitries along which brain areas function. In the past, comprehensive …