Plastics and Semantics

The Dynamic Neuron: A Comprehensive Survey of the Neurochemical Basis of Synaptic Plasticity By John Smythies Cambridge, MA: MIT Press (2002). 150 pp. $35.00To think of all the marvelous waysThey're using plastics nowadays.—Tom Lehrer A year ago I was designing a molecular neurobiology class and searching hard for a book that would synthesize this field for my students. Unhappy with the results of my hunt, I contacted a number of publishers, who all acknowledged the paucity of options. One even encouraged me to write a book, which unfortunately was not an option for this first year professor two months before classes began. I am happy to say my students and I survived the semester, but even with my extensive conglomerate of resources, we struggled through the topic of synaptic plasticity. Now finished with my visiting professorship, I have moved into a new field and a smaller apartment, so those books have been relegated to the basement. But now comes Smythies's new volume on synaptic plasticity, which could be my missing link for future classes. Upon reading The Dynamic Neuron, it has become clear why my students and I struggled with this topic; synaptic plasticity is an expansive field with a long history, studied by a growing population of researchers from many different backgrounds. And, quite frankly, it has a bad name.Early in my scientific career, I am embarrassed to admit that a dull, uncomfortable feeling washed over me whenever a friend told me that her favorite molecule has been shown to play a role in synaptic plasticity. I would smile and feign excitement, but wonder just what does her molecule do? I had a clear image of the “synapse” portion of “synaptic plasticity,” but as a child of the '70s, my vision was skewed by my concept of “plastic.” I was fixated on Tupperware and Rubbermaid containers of all shapes, sizes, and colors piled up in a dirty landfill, never degrading—I could not correlate this with synapses, dynamic neurons, and memory. But a trip to our semantic bible, the Oxford English Dictionary, remodeled “plastic” for me. It is not a modern term at all but was actually used as early as 1623. From the Greek plasto, to repair or plaster, came “plastic” as people began to use compounds such as resins, cellulose products, and even egg white products not only for patching and building, but also molding free-standing pieces. The first artificial plastics were developed around the turn of the 20th century, and the ease with which they could be molded and hold almost any shape amazed. Thus their indestructible path into our lives, landfills, and lexicon was cemented.While synthetic plastics were making waves in the early 1900s, Ramon y Cajal was busy describing the structural junction between two neurons, and the synapse was soon named (syn: together + haptein: to join). His contemporaries Spencer and Tanzi hypothesized that changes at the synapse might be involved in learning, and Cajal himself proposed the revolutionary idea that learning required neuronal growth. Smythies points out that the prevalent image of the central nervous system at that time was more like hardened mortar than clay, and certainly not dynamic. And so the phrase “synaptic plasticity” developed from this past era, influenced by a world excited about the molding of new chemical polymers, and just beginning to accept the idea that nerves themselves might be alterable.It was years before in vivo examples of these structural modifications gained widespread attention. Publication in the 1970s of a series of studies detailing the formation of ocular dominance columns in the brain fueled new areas of research. By injecting radioactive proline into a vertebrate eye, researchers learned that there is an activity-dependent pruning of synaptic connections during postnatal development, and elegant experiments grafting a third eye into a frog demonstrated that the formation of ocular dominance columns relies on target competition between synapses. The remodeling of neuronal junctions was thus shown to be an important part of development, but studies also demonstrated that these changes were limited to a “critical period” in life. Like most plastics, after being molded, their shape was set. Thus, it was not yet clear whether this work would be relevant to learning and memory in adults, where a model of an inert nervous system still prevailed. As Smythies points out in The Dynamic Neuron, the joining of biochemistry with neurobiology began as a slow process because of these preconceived notions, but as evidence mounted that cellular changes accompanied learning and memory, an onslaught of cellular and molecular research in these fields began.Electrophysiological studies of habituation implicated the synaptic connection in the learning paradigm, but the mechanisms controlling the strength of synaptic transmission were hard to dissect in early systems. Alterations might be pre- or postsynaptic, and could be chemical or structural. The entry of the soft and slippery sea slug Aplysia californica as a model organism revolutionized the study of synaptic remodeling by showing that combinations of all of the above mechanisms actually occur. By dissecting these “simple” neural circuits, Kandel and others joined neurobiology with the blossoming field of cellular biology and attracted many scientists to the study of learning at a molecular level. We now know that the signaling cassettes they uncovered function in various forms in numerous systems, adding to the complexity of the problem.While the Aplysia reflexes are controlled at serotenergic synapses, many of these signaling cassettes are conserved in vertebrate central nervous system synapses, largely glutamatergic. Modulation of AMPA and NMDA glutamate receptors have been under intense study in cultured neurons and hippocampal slices ever since lesions in the hippocampus were linked to amnesia. Long-term potentiation (LTP) in hippocampal circuits was discovered by Bliss and colleagues and promoted as a cellular model for vertebrate learning. The late stage of LTP, which may involve the splitting of dendritic spines and the formation of new synapses, has attracted tremendous numbers of molecular cellular biologists eager to play a role in understanding the brain. The excitement surrounding these studies is palpable, and the amount of data is overwhelming.It is into this stew that Smythies has jumped. In the preface he states his wishes to bring classic neurobiologists together with cell biologists in a contemporary work on synaptic plasticity, written for a general science audience. This well describes the type of approach that I sought for my students, and I had high hopes for the book. The slim volume is the perfect approachable size for a student or a scientist updating herself in the field. It is clear from the preface that he recognizes both the weaknesses in the field and the challenges that lay ahead as he attempts to bring the boil down to a simmer before the field “drowns in a sea of data.” Smythies's ambitions are laudable, and success would be a huge service to students and researchers alike, but ultimately he falls short of his challenging goals.Though one can sense Smythies's excitement in dissecting a biochemical pathway, the book itself often reads like a laundry list of molecules whose context in plasticity processes is not made clear. My semantic hang-ups concerning “synaptic plasticity” may be explained away by my era of upbringing, but it is clear that this phrase encompasses many processes that are certainly distinguishable, and yet the term is frequently used as a broad catch-all for potentially unrelated molecular events. Scientists have the tools to determine whether a molecule functions pre- or postsynaptically or in early or late LTP, and many researchers further narrow the field. If some of Smythies's resources fail to include this information, he would do better to leave them out. Furthermore, putting the molecules in their biological framework on the organismal level would be immensely helpful, as would explaining some of the studies from which a given work developed. Certainly this would make the book more useful to interested readers who lack a classical neurobiological training. I learned a number of interesting facts in reading this book, many of which are very current, but too often these ideas were buried next to loosely related material under chapter headings like “Special Proteins” and “Miscellaneous Items.” These problems could easily be fixed with some organizational editing in a later edition, which would make the material much more accessible. Such changes could render the work a very useful resource for readers from all aspects of the field, and for newcomers and students learning for the first time all the marvelous ways we're studying synaptic plasticity nowadays.