The diversity we must encompass in neuroscience is illustrated by recalling a few of the many important discoveries of the past few decades. Studies on the squid giant axon led to our understanding of the ionic basis of the action potential. Studies on the frog neuromuscular junction defined the process of chemical neurotransmission and the electric organ provided the molecular basis of ion channels. Biochemists used purified synaptic vesicles to identify every protein in these critical organelles, but yeast geneticists had the information needed to quickly understand the function of each protein. Patch clampers let us study individual ion channels and molecular biologists let us dissect the channels into working parts and relate genetic disorders to specific mutations in these channels. Cell biologists provided the tools that now let us watch activity-dependent alterations in neuronal morphology. Endocrinologists forced us to include steroid and thyroid hormones as important short and long term signaling molecules affecting neuronal function. Biochemical studies of second messenger systems revealed cross-talk and plasticity, factors contributing to signaling pattern complexity and perhaps underlying learning and memory. The visual system revealed the receptive field and topographical organization of sensory systems and the cortex gave us cortical barrels. Developmental neurobiologists showed us roles for multiple innervation and competition that we see as refinement of connections and plasticity in the adult central nervous system. The identified neuronal growth and survival factors provide hope for prevention of neuronal degeneration and controlled reinnervation.
What We Want Our Trainees to Learn
To appreciate and contribute to these many discoveries, from the earliest anatomical mapping to the latest gene cloning, scientists in the field of neuroscience need to have both a broad understanding of the historical background of the field, and what the key questions are today, where the field is going, and the key methodologies to reach the future goals. The goal of good neuroscience training is to prepare scientists for the next several decades of their careers, a truly daunting task.
The nervous system has laid down many hurdles for us, as if to make the task more fun and challenging: there are easily hundreds of cell types in the nervous system, more than in any other tissue; many neurons live for roughly the lifetime of the organism, again unlike most other tissues; and the functions of neurons can change dramatically over the lifespan of the organism.
Over the next few decades, a number of experimental preparation approaches will be very important, and we want our students to be ready to use these approaches and, more importantly, the as-yet-to-be-invented methods, and to have the knowledge needed to develop the next generation of approaches. With knowledge of their genomes complete, studies on C. elegans and Drosophila will reach a new level. Bioinformatics will be a key research tool available to all who have the skills to access the information. Mice expressing transgenes of interest and engineered for tissue-specific expression or lack or expression of specific genes will be essential tools. Proper use of these mice will require a variety of experimental approaches, ranging from behavioral to biochemical to anatomical and electrophysiological. Insight gained from crystallographic studies of key proteins will allow neuroscientists to probe specific protein-protein interactions in the proper cellular context and facilitate design of pharmaceutical compounds. New disease models will take us closer to studying human pathology and non-invasive methods and well-defined test questions will allow us to study humans as test subjects. Noninvasive optical methods will allow information to be gained about population averages of neurons in a way heretofore impossible. The critical, exciting, key experimental questions of today will merit intense discussion and investigation.
For our students, the ability to identify the critical questions of the future is essential. A broad background of knowledge, and a willingness to appreciate the insights gained from many different approaches, are key to this ability. These are attitudes that students acquire, almost unknowingly, from the faculty around them. Our faculty are excited about their own work. They are also interested in the work of their colleagues. They respect the contributions that can be made by psychophysicists, X-ray crystallographers, electrophysiologists, molecular biologists and anatomists and know that progress on the big questions requires the patient cooperation of outstanding researchers with diverse areas of expertise. Probably the key ingredient here is respect for contributions that come from the different approaches and a commitment to spanning the gaps between these seemingly disparate worlds.