Synapses (review)

Since its inception in 1970, the Society for Neuroscience has grown from a small company of 500 members to an unmanageable crowd of nearly 30,000. Knowledge of the basic unit of neural computation, the synapse, seems to have grown apace. Advances in electrophysiological techniques have allowed observations of synaptic events down to the level of fusion of individual presynaptic vesicles and to the opening of single post-synaptic channels. Molecular biology, in application to the nervous system, has identified a host of molecules forming the machinery of synaptic transmission. Publications describing the structure, composition, and physiology of synapses have multiplied beyond the limits of purview. Synapses broadly surveys this vast landscape of literature and scientific knowledge in relation to the basic signaling unit of the nervous system, the synapse. Such an overview tempts one to ask an imprudent question: are we approaching saturation in our knowledge of the nervous system?

In some respects, one is tempted to answer that we are. Major neurotransmitters and their receptors have been identified for most every tract of the nervous system. "Shotgun sequencing" and array-based screening of molecular libraries have allowed genome-wide surveys and forays into proteomics. Most of the molecular components of presynaptic release and post-synaptic signal transduction seem to be known. In fact, Südhof and Schaeffer, in their chapter on neurotransmitter release, boldly assert a near complete enumeration of the molecular players involved in synaptic vesicle fusion. One is reminded of the eminent physicist Lord Kelvin's fin de siècle assertion of the "end of Physics," famously posited on the eve of the quantum mechanics revolution. Despite such intimations of the end of neuroscience, a full reading of Synapses underscores that, although most of the molecules involved in conventional synaptic transmission may be identified, a much longer and more complicated journey remains to reach an understanding of how they all function together in an integrated nervous system.

This is an impressive book. The chapters cover every major area of study pertaining to synapses. Ranging from discussion of ultrastructural descriptions, to molecular characterizations of players in the fusion of vesicles, to the biology of synaptic cell adhesion, to rigorous physiological modeling of functional phenomenology, the individual chapters each provide thorough and clear summaries of related current knowledge. The editors, and the authors of the individual chapters, include many of the most prolific contributors to current progress in understanding of synapses, providing for surprisingly up-to-date reviews of the most recent developments. The chapters are well written and extensively referenced. Though some overlap in a book of this length and complexity is inevitable, there is surprisingly clean separation of focus between the chapters.

The book begins with a history of the understanding of synaptic transmission by Maxwell Cowan and Eric Kandel. The historical overview is written with a command of the facts that could only be offered by those well versed in the scientific issues and experimental approaches, having themselves participated in some of the important developments. One anecdote seems to provide a fitting parable to guide our approach to contemporary controversies. Their description of the decades-long "soup versus spark" debate, pitting chemical against electrical theories of synaptic transmission, brings to light an interesting example of the philosophy of science influencing and promoting scientific progress itself. John Eccles, a long-time proponent of the electrical theory of synaptic transmission, was influenced directly by Karl Popper's falsification doctrine, the view that scientific progress is fundamentally a process of constructing and experimentally testing hypotheses, and that good scientific models are those that provide falsifiable propositions. Eccles proceeded to propose and perform the key experiment that falsified his own view that central nervous system synaptic transmission was electrical.

From this enlightening start in the history of neuroscience, Synapses proceeds in a logical organization, through a description of the ultrastructural features underlying synaptic mechanisms, to a...