Studies on synapses

Sulzer works on basal ganglia and dopamine neurons, brain cells of central importance in translating will to action. His team have introduced new methods to study synapses, including the first means to measure the fundamental "quantal" unit of neurotransmitter release from central synapses. They reported the first direct recordings of quantal neurotransmitter release from brain synapses^[5] using an electrochemistry technique known as amperometry, based on the method of Mark Wightman, a chemist at the University of North Carolina, to measure release of adrenaline from adrenal chromaffin cells. They showed that the quantal event at dopamine synapses consisted of the release of about 3,000 dopamine molecules in about 100 nanoseconds.^[6] They further showed that the quantal events could "flicker" due to extremely rapid opening and closing of the a synaptic vesicle fusion pore (at rates as high as 4,000 times a second) with the plasma membrane.^[7] This approach also demonstrated that the "size" of the quanta could be altered in numerous ways, for example by the drug L-DOPA, a drug so used to treat Parkinson's disease.^[8]

Sulzer's lab, together with that of Dalibor Sames, a chemist at Columbia University, introduced "fluorescent false neurotransmitters", compounds that accumulated like genuine neurotransmitters into neurons and synaptic vesicles. This is used to observe neurotransmitter release and reuptake from individual synapses^[9] in video. Sulzer, along with his mentor Stephen Rayport, showed that the neurotransmitter glutamate is released from dopamine neurons,^[10][11] an important exception to the Dale's principle that a neuron releases the same transmitter from each of its synapses.

Addictive drugs

By introducing the "weak base hypothesis" of amphetamine action,^[12] for measuring amphetamine's effects on the quantal size of dopamine release,^[13] intracellular patch electrochemistry to measure dopamine levels in the cytosol,^[14] and providing real-time measurement of dopamine release by reverse transport,^[13] Sulzer's lab showed how amphetamine and methamphetamine release dopamine and other neurotransmitters^[15][16] and exert their synaptic and clinical effects. They showed how methamphetamine neurotoxicity occurs due to dopamine-derived oxidative stress in the cytosol followed by induction of autophagy,^[17] and with Nigel Bamford of the University of Washington, how these drugs activate long-term changes in the cortical synapses that project to the striatum.^[18] They call these "chronic postsynaptic depression" and "paradoxical presynaptic potentiation", which may explain drug dependence and addiction.

Sulzer explains in an interview on NOVA^[19] that his interest in understanding mechanisms of addiction stem from crashing a talk by William Burroughs at Naropa Institute in 1980, where Burroughs claimed that new synthetic opiates would be so powerful that users would become addicts with a single dose. In an interview in Nature Medicine on his lab's discovery of the mechanism by which nicotine filters synaptic noise and can focus attention to tasks, he recalls his father's early death due to smoking, saying "if some idiot or drug company is going to twist things around, the only thing that would come out of [this research] that I'd be horrified by is if people used it to advocate smoking. I think it would be a real travesty if that happened."^[20]

Neurological and psychiatric disease

Sulzer and his lab also studied nerve impulses in Parkinson's and Huntington's diseases, schizophrenia, drug addiction, and autism. They helped to establish the role of autophagy by lysosomes in neuronal disease.^[21] They showed the role of neuromelanin, the pigment of the substantia nigra,^[22] in methamphetamine neurotoxicity,^[17] and Huntington's disease.^[23][24] With Ana Maria Cuervo of Albert Einstein College of Medicine they showed that a cause of Parkinson's disease could be due to an interference with a chaperone-mediated autophagy caused by the protein alpha-synuclein.^[25][26] His work indicates that a lack of normal pruning of synapses could underlie the development of autism, and that in turn may also my due to inhibited neuronal autophagy in patients, due to overactivation of the mTOR pathway during childhood and adolescence.^[2]

In 2017, his lab introduced the role of autoimmune response in Parkinson's disease patients, which answers a century-old mystery on the role of immune system activation in that disorder.^[27]

The Sulzer lab has published over 250 papers on this research. For his work, Sulzer has received awards from the McKnight Foundation, the National Institute on Drug Abuse (NIDA), and NARSAD. He ran the Basic Neuroscience NIH / NIDA (T32) training program for postdoctoral research in basic neuroscience at Columbia. He received a Ph.D. in biology from Columbia University in 1988. He founded the Gordon Conference on Parkinson's Disease, the Dopamine Society (with Louis-Eric Trudeau) and the journal Nature Parkinson's Disease (with Ray Chaudhuri).

Awards and honors

2020 - Youdim / Finberg Award, Hebrew University, Jerusalem, Israel

2020 - Raymond D. Adams Lecture, Harvard University, Mass General Hospital, Boston, Massachusetts, USA

2019 - Distinguished Lecture in Medicinal Chemistry, University of Minnesota, USA

2017 - Presidential Lecture, Society of Neuroimmune Pharmacology

2013 - Helmsley Award for Scientific Research

2012 - Keynote Lecture in Cellular Neuroscience, Yale University, New Haven, Connecticut, USA

2008 - McKnight Award in Neuroscience for Technical Innovation

1996 - James T. Shannon Award, National Institute on Drug Abuse, National Institutes of Health, USA

Art and Science projects

Sulzer wrote a book on scientific principles that underlie music and sound "Music Math and Mind" [Columbia University Press], 2021), and teaches a related course at Columbia University on the physics and neuroscience of music and sound.

He co-ran the original science cafe, "Entertaining Science" from 2012 to 2019, with its founder (2002), chemist and writer Roald Hoffmann in Greenwich Village at the Cornelia Street Cafe .^[28]

With Brad Garton, he developed the "Brainwave Music Project", which allows users to create music from neural activity and enable teaching on brain function.

Music by animals

Many of Soldier's works are collaborative, such as with the Thai Elephant Orchestra which he co-founded with conservationist Richard Lair, based on the observation that elephants are said to enjoy listening to music.^[30] This ensemble consists of up to 14 elephants at the Thai Elephant Conservation Center near Lampang, and is listed by Guinness as the world's largest animal orchestra, with a combined weight of approximately 23 tonnes (50,706 lb).^[31] He built giant musical instruments on which he trained the elephants to improvise:^[32] they eventually played on 22 instruments. The orchestra has released three CDs and play an abbreviated concert daily at the Conservation Center.

He also created specially designed instruments for music played by zebra finches and bonobos, the latter in collaborations with physicist Gordon Shaw, who researched classical music's effect on the brain and introduced the Mozart effect.^[33]

Music by children

Soldier has made multiple recordings in which he coached child composers in different cultures. He and flutist Katie Down coached free improvisation with The Tangerine Awkestra featuring 2-10 year old Brooklyn schoolchildren. Da HipHop Raskalz featured rap and dub tracks performed (including the instrumental tracks) by 5-10 year old East Harlem children,^[34] who had no previous experience playing instruments. Sulzer and the santur player Alan Kushan produced Yol K'u with Mayan Indian children from the Seeds of Knowledge School in the high mountains of San Mateo Ixtatan, Guatemala, a collaboration using giant marimbas. He produced two CDs by Les Enfants des Tyabala, with the jazz musician Sylvian Leroux who coached children in Conakry, Guinea to form an ensemble and create works with the traditional Fula flute, which Leroux has adapted to play chromatic scales.

The Soldier String Quartet

In 1985 he founded the Soldier String Quartet, a punk chamber group that plays with amplification and a percussionist. As a leader, composer and violinist for the group, Soldier wrote and performed traditional pieces influenced by music styles including serialism, Delta blues and hip-hop. With inspiration from Haydn and Beethoven quartets, he explored anachronisms stemming from a classical ensemble playing in contemporary popular idioms, particularly rhythm and blues and punk rock. With a drummer incorporated into the quartet, Soldier found that string instruments could play the blues in the hands of players who understood the contrasting styles, including violinists Regina Carter and Todd Reynolds. The Soldier String Quartet also premiered and recorded works by other composers such as Elliott Sharp, Iannis Xenakis, Alvin Curran, Nicolas Collins, Butch Morris, Zeena Parkins, Leroy Jenkins and Phill Niblock, as well as with jazz musicians including Tony Williams and Amina Claudine Myers. They recorded with the rock and pop musicians Guided by Voices, Lambchop, Bob Neuwirth, Ric Ocasek, Van Dyke Parks, and Jesse Harris and were the touring and recording group for the Velvet Underground's John Cale from 1992 to 1998.

Experimental music

With Komar & Melamid, and inspired by their art project, "The People's Choice", Soldier wrote The People's Choice: Music, with lyrics by Nina Mankin. It was written according to answers from a survey of over 500 Americans, resulting in "The Most Wanted Song" and "The Most Unwanted Song". The latter is over 22 minutes in length and features an operatic soprano rapping cowboy songs, holiday songs with a children's choir screaming advertisements, and political rants backed by bagpipe, banjo, tuba, piccolo, and church organ.

Soldier collaborates with the computer musician Brad Garton for the Brainwave Music Project,^[35][36] creating music played by performer's brainwaves using electroencephalograms.

Soldier realized the request by Johannes Kepler for a specific motet as related 400 years earlier in Harmonices Mundi, also known as The Music of the Spheres, a foundational book for modern physics. This microtonal piece for six acapella singers, each portraying a different planet in the solar system, had not been realized before according to Kepler's specific instructions, and is recorded in three dimensional virtual reality sound by Drazen Bosnjak with the vocal group Ekmeles so that the planets revolve around the head of the listener. The resulting composition, "Motet: Harmony of the World", is co-credited to Kepler and Soldier.

He has a body of compositions using math derivations such as fractal manipulations, including a notorious 20 minute version of Chopin's Minute Waltz.

Concert music

Soldier's compositions with classical musicians include a socialist-realist opera, "Naked Revolution", based on paintings by the Russian conceptual artists Komar and Melamid, commissioned for the 25th anniversary of "The Kitchen".

The opera "The Eighth Hour of Amduat" uses as its text Italian translations of the ancient Egyptian of the book of Amduat and features Marshall Allen of the Sun Ra Arkestra playing the part of Sun Ra.

Soldier wrote two chamber operas in collaboration with author Kurt Vonnegut, "The Soldier's Story" and "Ice-9 Ballads", both recorded with Vonnegut playing characters in the operas.

Many of his chamber and orchestra works were recorded by the Manhattan Chamber Orchestra under conductor Richard Auldon Clark and by the Composer's Concordance orchestra. These include a collection of early Latin homoerotic lyrics in "Smut", and settings of Frederick Douglass in "The Apotheosis of John Brown" and Mark Twain in "War Prayer". The orchestra fanfare, "Samul Nori Overture", was commissioned by Kristjan Järvi and the Absolute Ensemble.

Chamber works by Soldier have been recorded by violinists Regina Carter and Miranda Cuckson, cellist Erik Friedlander, pianists Steven Beck, Taka Kigawa and Christopher O'Riley, accordionist William Schimmel, the PubliQuartet, singer Eliza Carthy, the choir Ekemeles, and flutist Robert Dick.

Rock music

Soldier performed in the early 1980s with Bo Diddley and founded The Kropotkins in the 1990s, a punk/country blues band with the Memphis singer Lorette Velvette and the drummers drummer, Moe Tucker of The Velvet Underground, Charles Burnham of the James Blood Ulmer's Odyssey Band, and Jonathan Kane of Swans and La Monte Young's band; the Kropotkins recorded four albums and developed a cult following. He continued collaborations with Jonathan Kane in a symphonic minimalist blues duo known as Soldier Kane.

In the early 1980s, Soldier played guitar with Bo Diddley and various rock groups. He later worked as an arranger, violinist, or guitarist with John Cale, Guided by Voices, Van Dyke Parks, David Byrne, Ric Ocasek, Lee Ranaldo, Eliza Carthy, Maureen Tucker, Laurie Anderson, the Plastic People of the Universe, Jesse Harris, Pete Seeger, Richard Hell, and Bob Neuwirth.

Soldier led the touring group for John Cale, consisting of the Soldier String Quartet and B. J. Cole from 1992 to 1996, writing the groups arrangements for tours and several CDs and films including for Cale's scores for the Andy Warhol films "Eat" and "Kiss": his metal violin playing is featured on "Heartbreak Hotel" on Fragments of a Rainy Season. He led an flamenco/Middle Eastern rock group, The Spinozas, featuring lyrics from Arabic and Hebrew poetry from medieval Andalusia released on the album "Zajal".

Jazz

Soldier recorded as a multi-instrumentalist with the William Hooker Trio with Sabir Mateen and Roy Campbell, and has performed and recorded with Leroy Jenkins, Henry Threadgill, drummer Tony Williams, Jonas Hellborg, Butch Morris, Jason Hwang, William Parker, Billy Bang, Marshall Allen of the Sun Ra Arkestra, Karl Berger, Teo Macero, Myra Melford, Michael Wolff and Amina Claudine Myers.

Production

Soldier co-founded the EEG Records (formerly Mulatta Records) label in 2000, for which he has produced a wide variety of recordings including contemporary flamenco music by Pedro Cortes, Texas singer/ songwriter Vince Bell with Bob Neuwirth, the 30 piece jazz string orchestra Spontaneous River by Jason Hwang, jazz drummer William Hooker, the traditional group Wofa from Guinea with American R&B musicians including Bernie Worrell; the jazz French horn virtuoso John Clark (musician), the New York-Iranian santur virtuoso Alan Kushan and released music by David First, two albums of Fula flute music by Sylvain Leroux with children in Conakry, Guinea, Memphis musician Alex Greene, Ursel Schlicht, and Twink.