Some early travails of tracing axonal pathways in the brain.

The first great flowering of neuroanatomy began about 1870, reached its height in the late 1880s and, with some notable exceptions, went into a marked decline during the two decades between the first and the second World Wars. In this essay I will relate some of my personal experiences during the early stages of a second flowering of neuroanatomy that began some fifty years ago and ultimately led to the multifaceted neuroanatomy we now know. My account begins in 1937, when I had just passed the preclinical examinations at the University of L&den, and had accepted a two-year student assistantship in the anatomy department. A student assistantship was a formidable commitment of time and effort, but it also, in addition to free tuition, provided a valuable fringe benefit: student assistants had access to the histology laboratory and, after receiving basic instruction in histological technique, were allowed to take on a research project of their own. I chose to acquaint myself with the rat brain, as it appeared in serial paraffin sections that I had stained alternately with toluidine blue for cell bodies and with the protargol staining method for nerve fibers published by David Bodian (1936) only the year before. The Bodian method was a great boon to neuroanatomy: it was the first technique to permit excellent, routine silver staining of nerve fibers in paraffin sections. That was a particular blessing to me, for paraffin sections were the only type of sections I then knew how to cut and handle. It should be mentioned here that the anatomy of the brain was not a popular research topic in the 1930s. In Europe, at least, the subject was widely regarded as already harvested to exhaustion, and hence hardly worth exploring further. The term “neuroanatomy” did not even exist; the subject was considered to be simply part of general anatomy. It was pursued as an active research subject in only a few anatomy departments, of which Leiden’s was not one. While slowly becoming better acquainted with the rat brain, I developed a particular interest in the hypothalamus. The literature appearing at that time provided ample reason for such an interest. The first publications of the Scharrers had just come out, reporting their astonishing observation that cells of the magnocellular nuclei of the hypothalamus combine neural with secretory characteristics. The laboratories of S. W. Ranson in Chicago and W. R. Hess in Zurich were reporting a steady stream