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Jay Goldberg, PhD

(1935-2019)
ARO Award of Merit, 1997

Jay M. Goldberg, Ph.D., age 83, passed away on Monday, June 17, 2019, in Chicago, IL.

Goldberg was a “powerhouse in neurophysiology,” according to his colleagues. He was, for decades, the leading authority on the vestibular system, which is essential for normal movement and equilibrium. His laboratory was the first to unravel a cluster of previously neglected sensory organs that feed crucial information about spatial orientation, motion, balance, and head position to the brain.  “Our goal,” according to his website, “is to understand the operation of the entire system in terms of its cellular components. To this end, a combined neurophysiological, morphological and behavioral approach is used. The research program ranges from biophysical studies of the isolated sensory organs to single-unit recordings.”

Goldberg enjoyed a long and prolific career. He published more than 70 papers and 30 books, chapters and reviews, and is best known for his pioneering studies of inner-ear function that revealed how animals, including dogs and humans, pinpoint where sounds come from and how they are perceived.  The first of these studies, led by Goldberg and Paul Brown, his postdoctoral fellow, focused on how binaural neurons in the ears of dogs respond to sound localization. In a landmark study, Goldberg and Brown discovered how binaural neurons in the superior olive nucleus (or hindbrain) allow an animal to localize sound left to right, proposing a computational mechanism, decades before the advent of the field of computational neuroscience.  This groundbreaking study, published in the J. of Neurophysiology 50 years ago, remains the fourth most-cited paper in any APS journal.

In the early 1970s, Goldberg and the late Cesár Fernández, initiated a study into the vestibular compartment of the inner ear. They intended to complete the project within a year, but it took decades. It became their life’s work. Together, the two authors mapped out the structures that enable animals, from turtles to monkeys, to perceive their orientation in space.  This second cluster of studies emphasized the simplicity and elegance of the authors’ analysis, their careful phrasing and reasoning, and the coherent picture that emerged by examining a pinball-like set of structures that respond to head movements.

The three groundbreaking studies, published in 1971, described the “first complete characterization of the physiology of the mammalian peripheral otolith system,” according to Dora Angelaki, PhD, professor of neuroscience at New York University, who praised their historic significance in 2005. “When combined, these papers constituted the seed for an explosion of quantitative studies on the properties of neurons in the central nervous system that detect and coordinate movement,” she wrote. These three papers “set the stage for vestibular system sensory function and launched a plethora of related quantitative studies during the decades to follow.”

“Goldberg and Fernández essentially figured out the vestibular system,” explained Peggy Mason, PhD, professor of neurobiology at UChicago, who was Goldberg’s colleague for years. “They created the field of vestibular physiology, starting from nothing.”  Goldberg was the chief editor of a new edition of a classic work on vestibular function, “The Vestibular System: A Sixth Sense”.  He catalogued a wide range of phenomena controlled by the vestibular system, ranging from how dancers and spinning ice skaters maintain their balance to how alcohol intoxication leads to vertigo.  His work opened up channels that explained “all sorts of unexpected results,” Mason added. He had a talent for making complicated ideas accessible, and he “wrote beautifully about what he and his colleagues discovered.” He was recruited to become a member of one of NASA’s Scientific Advisory Committees, working in the Vestibular Research Facility from 1984 to 1992, and he wrote the so-called “Goldberg Report,” setting out a strategic plan for life science research at NASA for the 1990s.

Born Nov. 9, 1935, Jay Myron Goldberg grew up on the West Side of Chicago. In 1952, at age 16, he entered University of Chicago. He graduated in 1956 with multiple honors in biochemistry, followed by four years in the biopsychology doctoral program.  He then enrolled in a post-doctoral program in biopsychology at the University of Wisconsin-Madison, with funding from the National Science Foundation and the National Institutes of Health.  Although his three years at Wisconsin made him a lifelong Green Bay Packers fan, Goldberg returned to Chicago in 1963 as an assistant professor of physiology. He stayed at UChicago for the rest of his career.  He quickly rose through the ranks.  He was promoted to associate professor in 1968 with a joint appointment in theoretical biology in 1969 and to professor in 1972.  Mentored at different stages of his career by two ARO Award of Merit winners, Jerzy Rose and W. Dewey Neff, Goldberg won the Award of Merit himself in 1997.

He became a mentor to nearly everyone in the field.

He was a “larger-than-life character, ‘Mr. Vestibular,’ for four decades,” said Anna Lysakowski, PhD, professor of anatomy and cell biology at the University of Illinois at Chicago. “He became a mentor to nearly everyone in the field. He was critically insightful, with a lot of scientific integrity. People sometimes got nervous around him, but they appreciated his guidance.”  Goldberg was deeply committed to research and teaching. “He was a true mentor for me,” recalled Mason. “He was unbelievably helpful, patient, generous and honest. He read every paper I wrote, every grant.”  He could be gruff and was not a gentle editor, but “he wanted us to succeed. That was his way of being kind,” she added. “If you look at the leading vestibular researchers across the country and to some extent the world, most, if not all, are the scientific children or grandchildren of Dr. Jay M. Goldberg.”

Goldberg had four children from a previous marriage, David, Susan, Nancy, Aaron, and a stepson, Peter, from his marriage to Florence Bonnick, who died in July 2018.  Besides his passion for sports, he and Florence also loved classical music and spent summer weeks in Santa Fe, New Mexico, enjoying the Santa Fe Opera and Santa Fe Chamber Music Festival.

A memorial service was held Oct. 17 on the University of Chicago campus at Bond Chapel.

Modified from an obituary written by John Easton for the University of Chicago website

Univ. of Chicago obituary:  http://www.uchicagomedicine.org/forefront/biological-sciences-articles/2019/june/jay-goldberg-phd-pioneer-in-understanding-the-vestibular-system

Bárány Society obituary:  http://barany2020.com/jay-goldberg-phd-pioneer-in-understanding-the-vestibular-system.php

 

I began studying the vestibular system during my dissertation research at the Università di Pavia with Professors Ivo Prigioni and GianCarlo Russo. I had two postdoctoral fellowships, first at the University of Rochester with Professor Christopher Holt and then at the University of Illinois at Chicago with Professors Jonathan Art and Jay Goldberg.

My research focuses on characterizing the biophysics of synaptic transmission between hair cells and primary afferents in the vestibular system. For many years an outstanding question in vestibular physiology was how the transduction current in the type I hair cell was sufficient, in the face of large conductances on at rest, to depolarize it to potentials necessary for conventional synaptic transmission with its unique afferent calyx.

In collaboration with Dr. Art, I overcame the technical challenges of simultaneously recording from type I hair cells and their enveloping calyx afferent to investigate this question. I was able to show that with depolarization of either hair cell or afferent, potassium ions accumulating in the cleft depolarize the synaptic partner. Conclusions from these studies are that due to the extended apposition between type I hair cell and its afferent, there are three modes of communication across the synapse. The slowest mode of transmission reflects the dynamic changes in potassium ion concentration in the cleft which follow the integral of the ongoing hair cell transduction current. The intermediate mode of transmission is indirectly a result of this potassium elevation which serves as the mechanism by which the hair cell potential is depolarized to levels necessary for calcium influx and the vesicle fusion typical of glutamatergic quanta. This increase in potassium concentration also depolarizes the afferent to potentials that allow the quantal EPSPs to trigger action potentials. The third and most rapid mode of transmission like the slow mode of transmission is bidirectional, and a current flowing out of either hair cell or afferent into the synaptic cleft will divide between a fraction flowing out into the bath, and a fraction flowing across the cleft into its synaptic partner.

The technical achievement of the dual electrode approach has enabled us to identify new facets of vestibular end organ synaptic physiology that in turn raise new questions and challenges for our field. I look forward with great excitement to the next chapter in my scientific story.

 

Charles C. Della Santina, PhD MD is a Professor of Otolaryngology – Head & Neck Surgery and Biomedical Engineering at the Johns Hopkins University School of Medicine, where he directs the Johns Hopkins Cochlear Implant Center and the Johns Hopkins Vestibular NeuroEngineering Laboratory.

As a practicing neurotologic surgeon, Dr. Della Santina specializes in treatment of middle ear, inner ear and auditory/vestibular nerve disorders. His clinical interests include restoration of hearing via cochlear implantation and management of patients who suffer from vestibular disorders, with a particular focus on helping individuals disabled by chronic postural instability and unsteady vision after bilateral loss of vestibular sensation. His laboratory’s research centers on basic and applied research supporting development of vestibular implants, which are medical devices intended to partially restore inner ear sensation of head movement. In addition to that work, his >90 publications include studies characterizing inner ear physiology and anatomy; describing novel clinical tests of vestibular function; and clarifying the effects of cochlear implantation, vestibular implantation, superior canal dehiscence syndrome and intratympanic gentamicin therapy on the inner ear and central nervous system.  Dr. Della Santina is also the founder and CEO/Chief Scientific Officer of Labyrinth Devices LLC, a company dedicated to bringing novel vestibular testing and implant technology into routine clinical care.

Andrew Griffith received his MD and PhD in Molecular Biophysics and Biochemistry from Yale University in 1992. He completed his general surgery internship and a residency in Otolaryngology-Head and Neck Surgery at the University of Michigan in 1998. He also completed a postdoctoral research fellowship in the Department of Human Genetics as part of his training at the University of Michigan. In 1998, he joined the Division of Intramural Research (DIR) in the National Institute on Deafness and Other Communication Disorders (NIDCD). He served as a senior investigator, the chief of the Molecular Biology and Genetics Section, the chief of the Otolaryngology Branch, and the director of the DIR, as well as the deputy director for Intramural Clinical Research across the NIH Intramural Research Program. His research program identifies and characterizes molecular and cellular mechanisms of normal and disordered hearing and balance in humans and mouse models. Two primary interests of his program have been hearing loss associated with enlargement of the vestibular aqueduct, and the function of TMC genes and proteins. The latter work lead to the discovery that the deafness gene product TMC1 is a component of the hair cell sensory transduction channel. Since July of 2020, he has served as the Senior Associate Dean of Research and a Professor of Otolaryngology and Physiology in the College of Medicine at the University of Tennessee Health Science Center.

Gwenaëlle S. G. Géléoc obtained a PhD in Sensory Neurobiology from the University of Sciences in Montpellier (France) in 1996. She performed part of her PhD training at the University of Sussex, UK where she characterized sensory transduction in vestibular hair cells and a performed a comparative study between vestibular and cochlear hair cells. Gwenaelle continued her training as an electrophysiologist at University College London studying outer hair cell motility and at Harvard Medical School studying modulation of mechanotransduction in vestibular hair cells. As an independent investigator at the University of Virginia, she expanded this work and characterized the developmental acquisition of sensory transduction in mouse vestibular hair cells, the developmental acquisition of voltage-sensitive conductances in vestibular hair cells and the tonotopic gradient in the acquisition of sensory transduction in the mouse cochlea. This work along with quantitative spatio-temporal studies performed on several hair cell mechanotransduction candidates lead her to TMC1 and 2 and long-term collaborations with Andrew Griffith and Jeff Holt. Dr. Géléoc is currently Assistant Professor of Otolaryngology, at Boston Children’s Hospital where she continues to study molecular players involved in the development and function of hair cells of the inner ear and develops new therapies for the treatment of deafness and balance, with a particular focus on Usher syndrome.

Jeff Holt earned a doctorate from the Department of Physiology at the University of Rochester in 1995 for his studies of inward rectifier potassium channels in saccular hair cells.  He went on to a post-doctoral position in the Neurobiology Department at Harvard Medical School and the Howard Hughes Medical Institute, where he characterized sensory transduction and adaptation in hair cells and developed a viral vector system to transfect cultured hair cells.  Dr. Holt’s first faculty position was in the Neuroscience Department at the University of Virginia.  In 2011 the lab moved to Boston Children’s Hospital / Harvard Medical School.  Dr. Holt is currently a Professor in the Departments of Otolaryngology and Neurology in the F.M. Kirby Neurobiology Center.  Dr. Holt and his team have been studying sensory transduction in auditory and vestibular hair cells over the past 20 years, with particular focus on TMC1 and TMC2 over the past 12 years.  This work lead to the discovery that TMC1 forms the hair cell transduction channel.  His work also focuses on development gene therapy strategies for genetic hearing loss.