This article is part of a series on Our Grandparents. See also:
- Irving Diamond: A Neuroscience Great Left Big Shoes Behind
- Ilya Dreyzen: A Faded Russian Hero
- Viktoria Dreyzen: Home of the Brave
- Michelle Diamond: Washington Prom
I never got to know my grandfather; he passed away from Alzheimer’s when I was young. Only later, after I developed my own interest in neuroscience, did I learn that Irving T. Diamond was a towering figure in the neuroscience world. I can only hope to someday equal his legacy—and I’m not just talking about his accomplishments in the laboratory. He was loved by his colleagues, students, family, and by the entire scientific community.
Irv, as he was affectionately called by his colleagues, earned a B.A. at Chicago, followed by a Ph.D. in psychology (back when psychology really meant cognitive neurobiology). In 1948, after completing his Ph.D., he accepted a permanent teaching position at Chicago. Among his students was John Jane, now chairman of the University of Virginia Department of Neurosurgery. Dr. Jane, who is now in his 80’s, remains a close family friend through today.
In 1958, Irving moved to Duke University, taking his students along with him. There, he and his students continued their groundbreaking research on visual and auditory perception in the mammalian neocortex. Among his findings was the discovery that the pulvinar nucleus of the tree shrew, traditionally considered an association cortex to the lateral geniculate nucleus (LGn), remained intact even after striatal ablation produced massive neurodegeneration in the LGn. Interestingly, the tree shrew also retained basic visual function (ability to distinguish between horizontal and vertical stripes) after this ablation. Only after the occipital cortex, another source of sensory input, was also ablated, did the pulvinar nucleus degenerate, along with the remainder of the shrew’s visual functionality. This suggested that the pulvinar nucleus ought instead to be called a sensory cortex rather than an association cortex, since it’s the target of a visual pathway, albeit one distinct from that which includes the LGn and striatum. 
Irving achieved similar and equally-groundbreaking discoveries in the auditory cortex, and altogether changed the way we understand the way mammals process sensory input. His grandeur, moreover, extended outside the laboratory.
Irving gave hundreds of talks around the world, and was well-received wherever he went. He met plenty of adventure, too. In China, he toured the Forbidden City with his fellow scientists, listening to stories about libraries pillaged, families separated, and lives lost during Mao Zedong’s 1966 Cultural Revolution. These accounts were given “with stoicism, resignation, and even good humor.”  In Russia, 1980, Irving drove for an hour, past grocery stores with lines two blocks long, to meet in secret with a fellow scientist, Adolph Lev. Only inside Lev’s crumbling apartment, with shades drawn, were they free to talk about their work without worrying about KGB intrusion. 
I visited Irving’s former student, Dr. John Jane Sr., in January, during the weekend of my interview at the UVa School of Medicine. He told me a story about Irving, who had just given a talk in Rome. “He was sitting at the head of the dinner table, talking to two pretty girls, one on either side. He was more of a charmer than I ever was.” We both had a good laugh, but then I saw a shimmer in Dr. Jane’s eye.
My grandfather made a profound impression on everyone he met. Late in his life, a Society for Neuroscience meeting was given in his honor. This meeting featured presentations given by all his former students. “This event was the highest moment of my career,” Irving said of the event. “I was touched and delighted, as were my children who attended, Mathew, Nancy, and Thomas.”  (Nancy is my mom!)
Establishing a scientific impact even close to Irving’s is a great hope of mine. My current research is actually going pretty well. I’ve just started working on my senior thesis, which could get published.
Our lab studies two main phenomena: homeostatic synaptic plasticity (HSP) and sleep. HSP refers to a rapid compensatory process at the synapse; it occurs in all animals, but we study it in Drosophila (the fruit fly). Shortly (10 min) after the introduction of some postsynaptic glutamate receptor antagonist at the neuromuscular junction (NMJ), one can observe a compensatory increase in vesicle fusion in the presynaptic neuron. Philanthoxin, which comes from bee venom, is a good example. 10 minutes after introducing philanthotoxin at the NMJ, the presynaptic motor neuron will begin releasing more glutamate into the synapse. Somehow, presumably due to some sort of retrograde signal, the presynaptic neuron knows that the postsynaptic receptors have decreased in sensitivity.
The research, then, largely concerns certain genetic mutants in which this HSP process fails. Following introduction of philanthotoxin, there’s no compensatory increase in vesicle release in these mutants. Adding to the interest is the fact that one of the main HSP mutants, dysbindin, carries a gene mutation similar to one which, in humans, is associated with schizophrenia. So, the idea is that schizophrenia and other neuropsychiatric disorders in humans might stem directly from HSP dysfunction.
The other facet of the lab, which is headed up largely by me, studies sleep. The interest in sleep began when another HSP mutant was discovered at random from a large-scale genetic screen. Upon searching for information on this gene, we learned that the mutant, dubbed minisleep, was known in the literature as a sleep mutant.  Minisleep demonstrates decreased total sleep time per 24 hours, and also disorganized sleep—shorter sleep bouts, more frequent “naps,” and a seemingly-random sleep schedule throughout the 24-hour period. Thus the connection between HSP dysfunction and sleep dysfunction was born. And it makes a lot of sense: consider that those suffering from neuropsychiatric disorders often experience sleep problems (or is it the other way around?).
My task in the lab has been to explore the HSP-sleep connection. It turns out that dysbindin also demonstrates a sleep phenotype, though perhaps not quite as robust as minisleep. Another interesting result came just last week. dGRASP, another HSP mutant, actually seems to sleep more than a healthy animal.
How might this be explained? Well, one possible theory posits that sleep’s role is metahomeostatic: sleep actually modulates HSP, which itself is a homeostatic process. Perhaps HSP function progressively declines during waking, and sleep’s role is to correct this. In fact, declining HSP function might produce the need to sleep. Thus, it makes sense that, in animals in which sleep is inherently broken, HSP would be disrupted too, since sleep allows for HSP to occur. But in an animal in which HSP was inherently broken, the need to sleep would be amplified.
So, in dysbindin and minisleep, it seems that sleep might be inherently disrupted, whereas in dGRASP, HSP might be inherently disrupted. This could explain why all demonstrate an HSP phenotype, but, while the former two sleep less, the latter sleeps more.
Of course, a lot more evidence would be necessary to rigorously support this theory. All things considered, though, my research is going well. Perhaps it’s not inconceivable that, someday, a Society for Neuroscience meeting might be given in my honor.
As for my grandfather’s irresistible charm? Well, I’m working on that too.
- Chapter on Irving T. Diamond, written by Irving T. Diamond. Excerpt from A History of Neuroscience in Autobiography.
- Paper by my principle investigator, Dion Dickman. The schizophrenia susceptibility gene dysbindin controls synaptic homeostasis
- Minisleep paper. Reduced sleep in Drosophila Shaker mutants