The successful aging of Carl Cotman: from proteins of the synapse, through sprouting, regeneration, and spinal cord injury to the mechanisms of brain aging.

I have a ﬂash-bulb memory of the ﬁrst time I spoketo Carl Cotman in May, 1970. I had applied to the gradu-ate program of the Department of Psychobiology at UCIrvine (my ﬁrst choice for graduate school) and had notbeen accepted in the ﬁrst round. I had resigned myself toattending graduate school elsewhere, but received a callfrom Carl one evening. Carl spoke with his characteris-tic candor, which can be either charming or intimidating(in this case, it was intimidating). He said that my cre-dentials weren’t all that great, but he liked the fact thatI had completed my undergraduate studies at the Uni-versity of Colorado in 3 years while supporting myselfthrough part-time jobs—hence the phone interview. Isweated bullets through the interview, and in the end, heoffered me a position in his lab. His decision to give mea chance highlights two features of his personality—hiswillingness to take risks and his personal ethic for hardwork. I don’t think that he had too many occasions toregret his decision, although he probably had some sec-ond thoughts during the early part of my graduate career.I joined Carl’s lab in the fall of 1970 at the start ofCarl’s third year at UCI. By that time, four other studentswere in the lab, included Gary Banker, William (Chip)Levy, Dee Ann Matthews, and Lynn Churchill. The cal-dron of Carl’s lab and the wonderfully intense graduateprogram in the department forged friendships and fos-tered collaborations that have lasted a lifetime. In fact,the University of Virginia later became an outpost ofCarl’s former trainees when I recruited Chip Levy to theDepartment of Neurosurgery and Gary Banker to thenewly established Department of Neuroscience.When I joined Carl’s lab, the main focus of researchwas on the chemistry of the synaptic junction. EachMonday morning started with the collection of rat brains(40 or so) for subcellular fractionation experiments.Everyone participated in this Monday morning “brainsand donuts” collection process. This was really nuts andbolts neurochemistry and led to fundamental, indeedlandmark, discoveries about the structure and proteincomposition of the synaptic junctional complex (1,2).The subcellular fractionation techniques he developed forisolating postsynaptic densities (psds) are still in usetoday, and the psd, which he identiﬁed as a deﬁnableand isolatable structure, has come to be recognized asa highly organized collection of interrelated signalingmolecules (3).At about the time that I joined the lab, Carl wastrying different approaches to begin to address broaderquestions of synaptic function, especially synaptic plas-ticity. It is remarkable how many important scientiﬁcthreads can be traced from his work during that period.My ﬁrst project in the lab was to try to determinewhether synaptic activation altered protein synthesis inpostsynaptic cells (what we would now call synapticregulation of gene expression). Carl’s idea was to usethe abdominal ganglion of aplysia as a model for stud-ies of synaptic biochemistry. The experiment was toactivate connectives that contained nerves that synapsedon the large R60 neuron in the ganglion in the presenceof labeled amino acids, then dissect out the large R60neuron and assess incorporation into protein usingmicrobiochemical techniques. At that time, we collectedthe experimental animals ourselves in outings to the tidepools off Crystal Cove near Irvine. Fortunately, Carl didnot go on these outings and did not seem to be awareof the tide tables that limited collection times. Thus thecollection party (the graduate students in the lab)planned the day so as to collect the necessary specimens