Dr. Sulzer’s lab investigates the function and alteration of the synapses of the cortex and the basal ganglia including the dopamine system in normal behaviors such as habit formation and action selection, and in diseases of the system. Their work has made fundamental contributions to understanding the roles of these synapses in Parkinson’s and Huntington’s diseases, schizophrenia, autism, and drug addiction. His laboratory developed new optical, electrophysiological and electrochemical methods including the first direct recordings of quantal neurotransmitter release from synapses, the fundamental unit of neurotransmission, and the first optical methods to observe neurotransmitter release and reuptake. His work increased the understanding of the life cycle of synaptic vesicles, cellular structures that package neurotransmitter release. (source: Columbia)
In addition to his day job as a neuroscientist, Dr. Sulzer is also an accomplished musician. He played guitar in Bo Diddley’s band, engaged in multiple collaborations with the Russian conceptual artists Komar and Melamid, and co-wrote two operas with Kurt Vonnegut. He studied composition with Otto Luening and formed his Soldier String Quartet in 1985. He co-founded Mulatta Records in 2000 to document his projects, including the Thai Elephant Orchestra, a group of 14 elephants playing instruments in northern Thailand, and produced a broad range of artists in unusual musical styles. Sulzer performed, recorded, composed, and arranged for television and film (Sesame Street, I Shot Andy Warhol), and pop and jazz acts ranging from Pete Seeger to David Byrne and Guided by Voices.
Here he is in the trailer to the PBS documentary on his famed elephant orchestra…
The following has been condensed and paraphrased from an interview with Prof. David Sulzer on October 30th, 2018.
(Click above to listen to the full audio version or click here for a downloadable version)
Where did your interest in elephants come from?
Some friends (satirical painters Komar & Melamid) found out about the plight of elephants in Thailand who had lost their jobs in the lumber industry and were no longer receiving proper care. They heard that elephants can be taught to paint, so they went over there and trained elephants to do exactly that. This created a mini-industry of people selling elephant paintings which helped lead to the first elephant conservation center (the Thai Elephant Conservation Center in Lampang).
When I went there for the first time in 2000 it still wasn’t very well established and they were looking for more ways to get people and local governments to care about the elephants. We (with Richard Lair, and American conservationists who worked at the Center) looked for something that elephants would enjoy doing and that was also social because they like doing things in groups. Well, they enjoy listening to music so we built giant instruments which they learned to play within five minutes.
How has your work with elephants changed your understanding of what intelligence is?
We are proud when our dogs can understand five or six commands, but people who grow up with elephants will tell you that they can comprehend about as much as a six year old human. They can understand very complicated verbal commands like ‘take all these logs and arrange them in a pyramid shape’. Elephant societies are also extraordinarily complex, they teach each other all the time and have complex social relationships with each other and with us. They treat us as individual personalities and they each have their own as well, some are murderous and some will literally babysit a human baby.
So what is the difference between us and elephants? I think part of it is just we have language, however even there they have certain ways of communicating that we don’t. One example is they can produce frequencies that we can’t hear but which can travel miles to communicate with each other. They also have a sense of humor and even use it when interacting with us.
Jumping to the other end of the intelligence spectrum, why did you choose to study synapses?
I am also a musician and I was on tour in Boulder, Colorado where I went to a talk by the beatnik author William Burroughs. He was a heroin and morphine addict and I found his talk on addiction so fascinating that when the chance came to work in neuroscience I jumped at it. As for synapses per se, they are what makes the brain special, it is these connections between cells that allows us to do everything that we do.
But we have learned that there are single celled organisms with no synapses, like pond scum (Chlamydamonoas) that are extraordinarily adaptable. They eat light through photosynthesis but they can also live off electricity. They also have special proteins that allow them to see, they chase things, some of them have sex, all with a single cell. So there are a lot of things that can be done without synapses. But to get the higher order complex behaviors and movements you do need synapses.
Synapses are life’s way of sending messages from one place to another. How do you think nature ‘figured out’ how to do this?
Well it is not required for multicellular life, sponges don’t have synapses. But if you want to move muscles together for swimming let’s say, you will need something like a synapse for coordination. We are used to thinking about chemical synapses, however there are electrical synapses as well. You could imagine that more reliance on electrical synapses using ions and electrons instead of neurotransmitters could have also created a different form of evolution. That could have happened on other planets, but here chemical neurotransmitters dominate.
Could you talk about using neuromelanin imaging to detect and measure Parkinson’s disease?
I think this might be the most important conversation the Parkinson’s community can have at this time. This is my opinion and other people can and should argue against it but I think it is critical and it is one that often gets swept under the rug.
By the time people show up in the clinic with PD, they have already lost a large fraction of their neurons in the substantia nigra. However, what if we came up with a neuroprotective treatment that could slow down the progression of the disease by say 50%? That would be remarkable because it would extend the decline that happens now in 10 years to 20 years. But by the time symptoms are severe enough that they show up in the clinic, it becomes difficult to measure any slowing down in further neuronal cell death. We have developed a lot of neuroprotective strategies and I think we may already have medications that work, but because we start in this late stage of this disease we may not be able to prove it.
Thus we need to focus more on early detection. There are numerous ways out there that might be able to do this, but to me the clearest one is to examine neuromelanin by MRI. We all start of as babies with no visible neuromelanin, it becomes visible around the age of five and then it increases all the way to the age of 100. Neuromelanin also has resonance that can be measured by MRI. We advocated for this approach to anyone who would listen, unfortunately the inherent conservatism of the field made it difficult for anyone to support it. But if, after the age of 40, we started to routinely measure everyone’s neuromelanin we would know who is at risk of developing PD much earlier and be able to start applying therapies earlier. There are some technical improvements that still need to be made and we need to do more longitudinal studies but we are close to making this feasible.
Additionally, right now we have a whole bunch of disorders that are grouped under the name PD but they are really different diseases that we don’t have names for and which we might have to treat differently. Right now we just test for them using a crude motor scoring system, neuromelanin imaging could be a huge leap forward in helping us test if a treatment is working in an individual.
The prevailing belief in the community is that once neurons are gone they don’t grow back, could you talk about your work trying to regrow neurons and how D-serine might play into this?
First some interesting details about dopamine neurons. They are ancient and were first found in an extinct species of worm that is the ancestor to a wide variety of life, including us. (Click here to learn more) Something else I like to mention is the stuff that turns black in bananas is dopamine, while the black color in olives is made from L-dopa. One other particularly striking detail of dopamine neurons is they have the longest axons in the body, in mice one dopamine neuron can be half a meter in length, much longer than the mouse itself.
(Click above to hear a piece produced using brainwave sensors, courtesy of Dr. Sulzer’s Brainwave Music Project)
I had a very good post-doc in my lab named Yvonne Schmitz who wanted to figure out how dopamine neurons know where to grow. The dopamine axons have growth cones that detect all sorts of chemical signals that help them decide where they are going to grow. Even in advanced PD there is still a lot of dopamine neurons left, they are just in different parts of the brain. So the idea is, could we get these neurons to grow to the parts of the brain where dopamine is reduced in people with PD? We found that some of the binding sights use a weird amino acid called D-serine that could do the trick. D-serine has been used for years in health food stores and we are trying to move forward with a trial to test if D-serine could restore neuronal growth. This is exciting because in contrast to neuroprotective therapies, neurorestorative therapies would be much easier to measure and detect efficacy. It won’t be a cure, but in combination with neuroprotective treatments, these kind of neurorestorative therapies could significantly improve quality of life for people with PD.
Click here to learn more about the work of Prof. David Sulzer
and click here read to read from Nature npg’s Parkinson’s Disease journal which Prof. Sulzer started with Prof. Ray Chaudhuri as a free access journal open to everyone in the field.
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