Mechanisms of Synaptic Transmission: Bridging the Gaps (1890-1990) (review)

This book describes the long arc of human achievement in a key subdiscipline of neuroscience during the century that culminated in the "decade of the brain." By concentrating on the biology of the synapse, Joseph Robinson reviews developments from the "proclamation of the neuron theory" by Cajal to the era of Prozac, through the succinct citation of critical experiments.

Professor Robinson lets the science tell the story; biographical detail is spare, the distinguished exception being Ramon y Cajal. The technical limitations of light microscopy challenged investigators of the late nineteenth century, but the energetic Cajal responded by persistently improving methods of histological preparation. A tireless refiner of the techniques of others, Cajal improved and standardized Golgi's stain, and then used it to refute Golgi's concept of the nervous system as a reticular network, establishing instead that the neuronal population comprises discrete microscopic entities. He went on to demonstrate how "function follows form" by inferring from neuronal morphology the directionality of propagated impulses from dendrite through perikaryon, to the axon. Time has hardly tempered the irony that when Cajal and Golgi were joint recipients of the Nobel Prize in 1906, their Nobel lectures presented conflicting views of the field to which they had contributed so richly.

While their work continued to be debated, Charles Sherrington, another great neuroscientist closely connected to Cajal, steered the field from debates on microanatomy toward physiological experimentation. Once the concept of cellular integrity was established, defining cell boundaries became a challenge for anatomists, and ascertaining the means of cell-to-cell communication a mission for physiologists. Sherrington grasped the integrative nature of the nervous system, making this the focus of his career in research, and describing how the nervous system integrates reflexes, governs muscle tone, and maintains body posture.

The story of the discovery of the chemical basis of synaptic transmission begins with the remarkable experiment that Otto Loewi conceived in a dream, and extends through a sequence of critical experiments, including those of John Carew Eccles who, influenced by his colleague Karl Popper, tested hypotheses for purely electrical conduction, eventually refuting his own view. The development of electron microscopy, interrupted by World War II and requiring some years of technical refinement, eventually permitted visualization of the synaptic cleft and also helped explain how neurotransmitters are stored and released.

In an era of hypothesis-driven research, it is remarkable how many key discoveries occurred when "chance favored prepared minds." The beneficial effects of lithium were discovered serendipitously, during a study of hypothesized toxic effects of urea. Robinson also notes that new medicines for depression were identified through clinical observations of drugs expected to have other actions (iproniazid, imipramine).

This superb book provides a connecting thread through the long passage of clinical and experimental observations that have taken us from late nineteenth-century neurology to early twenty-first-century neuroscience. In reviewing these experiments, Professor Robinson shows that technical excellence is one of the forces enabling the ultimate consensus toward which scientific effort is inherently pushed. Although legions of key experiments reported over the past century often presented conflicting results, it was through further experimentation, extended discussion, and thoughtful review that the information became integrated into the larger discourse. Science is indeed a social enterprise capable of reconciling contradictions and refining perceptions into common knowledge, and in so doing it provides an outlet for belief in progress and the betterment of humankind.