The Highstein Vestibular Laboratory

The MBL community was saddened by the passing of Stephen M. Highstein, M.D., Ph.D., on January 22, 2014. Steve Highstein first came to the MBL in 1973 as a visiting scientist, initially collaborating with Michael Bennett of Albert Einstein College of Medicine. He returned to the MBL every summer thereafter to pursue his lifelong scientific study of the vestibular system in the toadfish (Opsansus tau) while serving as a professor of neuroscience at Albert Einstein College of Medicine and, later at Washington University in St. Louis. He moved his laboratory full-time to Woods Hole in 2009 as an MBL senior scientist and in 2012 he became associate director of the MBL’s new Program in Sensory Physiology and Behavior.

Steve Highstein was a consummately dedicated scientist, experimentalist and clinician. Under the mentorship of Bernard Cohen (Mt. Sinai School of Medicine) and Masao Ito (University of Tokyo), his early career focused on the control of eye movements. This effort continued in close collaboration with his lifelong colleague, Robert Baker (New York University Medical School), and their numerous students to elaborate understanding of the detailed structure/ function of the underlying brainstem and cerebellar circuitry. Subsequently, Steve’s collaborative team at Washington University, principally Pablo Blazquez (Washington University) and Yutaka Hirata (Chubu University), identified the organizational principles underlying circuit-level computations in cerebellar pathways which candidly addressed existing models, particularly those that did not include brainstem sites for plasticity.

Highstein’s laboratory at the MBL studied the vestibular organs of the inner ear that are responsible for both balance and posture in all vertebrates. He and his colleagues employed a wide variety of species for their experiments, from fish through turtles and mice, that took advantage of the state-of-art electrophysiological, video, neurochemical, and genetic techniques available at the MBL. As one example, Highstein’s work received much public recognition in 1998 when one of his toadfish experiments went into space with astronaut John Glenn and NASA’s NeuroLab shuttle mission. The toadfish vestibular neurons were wired with electrodes to record their response to the lack of normal gravitational stimulus. The experiments demonstrated that the fish’s inner ear “turned up” its sensitivity while in space, looking for the missing gravitational signal. This observation fundamentally confirmed the hypothesis that motion sickness in space, or space adaptation syndrome, is caused by a mismatch between an inappropriate inner-ear signal regarding gravity conflicting with other vestibular and visual signals.

Highstein’s work over the past decade at the MBL with Richard Rabbitt (University of Utah) Mary Anne Mann (MBL), Richard Boyle (NASA) and Gay Holstein (Mt. Sinai) focused on fundamental biological mechanisms responsible for the exquisite sensitivity of the inner-ear hair cell organs. His most recent work revealed a role for GABA in signal processing by the angular-motion sensitive semicircular canals, and uncovered evidence that protons transmit information from mechanosensitive hair cells to the brain via a unique and highly efficient calyx afferent synapse.

Steve lived every day of his life to the fullest with an outpouring of enthusiasm and energy directed toward science, art, friends, and the everyday pleasures of life.  He was a dedicated friend and colleague, a loving father and husband, and a strong advocate supporting the careers and lives of young scientists and students.  He will be remembered for his positive contributions to science, and for the love, support and mentorship he gave to the countless people he touched.

Stephen M. Highstein—CV and Selected Publications


1961, B.S. Biology, Rensselaer Polytechnic Insitute
1965, M.D. Medicine, University of Maryland Medical School
1976, Ph.D. Physiology, University of Tokyo Faculty Medicine

Experience, Positions, Appointments

1962: Summer Fellow, Dept. of Biology, California Institute of Technology
1963 – 1964: Co-worker, Physiology, Univ. of Maryland, Baltimore, MD
1965 – 1966: Intern in Medicine, Maimonides Hospital, Brooklyn, NY
1966 – 1969: Resident in Neurology, Mt. Sinai Hospital, NY, NY
1974 – 1976: Assistant Professor, Neuroscience, Albert Einstein College of Medicine, NY
1976 – 1981: Associate Professor, Neuroscience, Albert Einstein College of Medicine, NY
1981 – 1983: Professor of Neuroscience, Albert Einstein College of Medicine, NY
1983 – 2009: Professor, Otolaryngology, Anatomy & Neurobiology, Washington University School of Medicine, St. Louis
2009 – 2014: Senior Scientist, Marine Biological Laboratory, Woods Hole, MA

Selected Peer-Reviewed Publications

Highstein S, Cohen B, and Mones R. Changes in saccadic eye movements of patients with Parkinson’s disease before and after L-dopa. Trans Am Neurol Assoc 94: 277-279, 1969.

Ito M, Highstein SM, and Fukuda J. Cerebellar inhibition of the vestibulo-ocular reflex in rabbit and cat and its blockage by picrotoxin. Brain Res 17: 524-526, 1970a.

Highstein SM, and Ito M. Differential localization within the vestibular nuclear complex of the inhibitory and excitatory cells innervating 3d nucleus oculomotor neurons in rabbit. Brain Res 29: 358-362, 1971.

Highstein SM, Ito M, and Tsuchiya T. Synaptic linkage in the vestibulo-ocular reflex pathway of rabbit. Exp Brain Res 113: 306-326, 1971.

Highstein SM, Cohen B, and Matsunami K. Monosynaptic projections from the pontine reticular formation to the 3rd nucleus in the cat. Brain Res 75: 340-344, 1974.

Highstein SM, and Bennett MV. Fatigue and recovery of transmission at the Mauthner fiber-giant fiber synapse of the hatchetfish. Brain Res 98: 229-242, 1975.

Maciewicz RJ, Kaneko CR, Highstein SM, and Baker R. Morphophysiological identification of interneurons in the oculomotor nucleus that project to the abducens nucleus in the cat. Brain Res 96: 60-65, 1975.

Model PG, Highstein SM, and Bennett MV. Depletion of vesicles and fatigue of transmission at a vertebrate central synapse. Brain Res 98: 209-228, 1975.

Highstein SM, and Baker R. Organization of the efferent vestibular nuclei and nerves of the toadfish, Opsanus tau. J Comp Neurol 243: 309-325, 1986.

Strassman A, Highstein SM, and McCrea RA. Anatomy and physiology of saccadic burst neurons in the alert squirrel monkey. I. Excitatory burst neurons. J Comp Neurol 249: 337-357, 1986a.

Strassman A, Highstein SM, and McCrea RA. Anatomy and physiology of saccadic burst neurons in the alert squirrel monkey. II. Inhibitory burst neurons. J Comp Neurol 249: 358-380, 1986b.

Strassman A, Evinger C, McCrea RA, Baker RG, and Highstein SM. Anatomy and physiology of intracellularly labelled omnipause neurons in the cat and squirrel monkey. Exp Brain Res 67: 436-440, 1987.

Moschovakis AK, Scudder CA, and Highstein SM. A structural basis for Hering’s law: projections to extraocular motoneurons. Science 248: 1118-1119, 1990.

Moschovakis AK, Scudder CA, and Highstein SM. Structure of the primate oculomotor burst generator. I. Medium-lead burst neurons with upward on-directions. J Neurophysiol 65: 203-217, 1991.

Tricas TC, and Highstein SM. Action of the octavolateralis efferent system upon the lateral line of free-swimming toadfish, Opsanus tau. J Comp Physiol [A] 169: 25-37, 1991.

Highstein SM, Kitch R, Carey J, and Baker R. Anatomical organization of the brainstem octavolateralis area of the oyster toadfish, Opsanus tau. J Comp Neurol 319: 501-518, 1992.

Rabbitt RD Boyle R Highstein SM Mechanical indentation of the vestibular labyrinth and its relationship to head rotation in the toadfish, Opsanus tau. J Neurophysiol 73: 2237-2260 1995.

Highstein SM Rabbitt RD Boyle R. Determinants of semicircular canal response dynamics in the toadfish, Opsanus tau. J Neurophysiol 75: 575-596 1996.

Mensinger AF, Carey JP, Boyle R, Highstein SM. Differential central projections of physiologically characterized horizontal semicircular canal vestibular afferents in the toadfish Opsanus tau. J Comp Neurol 384:71-85 1997.

Highstein SM, and Cohen B. Neurolab mission. Curr Opin Neurobiol 9: 495-499, 1999.

Mensinger AF, Highstein SM. Characteristics of regenerating horizontal semicircular canal afferent and efferent fibers in the toadfish, Opsanus tau. J Comp Neurol 410:653-676 1999.

Rabbitt RD, Boyle R, Highstein SM. Influence of surgical plugging on horizontal semicircular canal mechanics and afferent response dynamics. J Neurophysiol 82:1033-1053 1999.

Edds-Walton PL Fay RR Highstein SM Dendritic arbors and central projections of physiologically characterized auditory fibers from the saccule of the toadfish, Opsanus tau. J Comp Neurol 411:212-238 1999.

Mensinger AF, Anderson DJ, Buchko CJ, Johnson MA, Martin DC, Tresco PA, Silver RB, Highstein SM. Chronic Recording of Regenerating VIIIth Nerve Axons With a Sieve Electrode. J Neurophysiol :83 611-615 2000.

Hirata Y, and Highstein SM. Acute adaptation of the vestibuloocular reflex: signal processing by floccular and ventral parafloccular Purkinje cells. J Neurophysiol 85: 2267-2288, 2001.

Boyle R, Mensinger AF, Yoshida K, Usui S, Intravaia A ,Tricas T, Highstein SM. Neural Readaptation to Earth’s Gravity Following Return from Space. J Neurophysiol 86: 2118-2122 ,2001.

Yamauchi A, Rabbitt RD, Boyle R, Highstein SM. Relationship between inner-ear fluid pressure and semicircular canal afferent nerve discharge. JARO 3: 26-44 2001.

Boyle R, Highstein SM, Carey JP, Xu JP. Functional recovery of anterior semicircular canal afferents following hair cell regeneration in birds. JARO 3:149-166 2002.

Blazquez PM, Hirata Y, Heiney SA, Green AM, and Highstein SM. Cerebellar signatures of vestibulo-ocular reflex motor learning. J Neurosci 23: 9742-9751, 2003.

Holstein GR, Martinelli GP, Henderson SC,Friedrich VL Jr., Rabbitt RD, Highstein SM. Gamma-aminobutyric acid is present in a spatially discrete subpopulation of hair cells in the crista ampullaris of the toadfish Opsanus tau. J Comp Neurol: 471 1-10, 2004.

Holstein GR, Rabbitt RD, Martinelli GP, Friedrich VL Jr., Boyle RD, Highstein SM. Convergence of excitatory and inhibitory hair cell transmitters shapes vestibular afferent responses. PNAS 101: 15766-15771 2004.

Holstein GR, Martinelli GP, Boyle RD, Rabbitt RD, Highstein SM. Ultrastructural observations of efferent terminals in the crista Ampullaris of the toadfish, Opsanus tau. Exp brain Res 155: 265-273 2004.

Rabbitt RD, Boyle R, Holstein GR, Highstein SM. Hair-Cell versus Afferent Adaptation in the Semicircular Canals. J Neurophysiol 93: 424-436 2005.

Highstein SM, Rabbitt RD ,Holstein GR, Boyle R. Determinants of spatial and temporal coding by semicircular canal afferents. J Neurophysiol 93: 2359-2370, 2005.

Blazquez PM, Hirata Y, and Highstein SM. Chronic changes in inputs to dorsal Y neurons accompany VOR motor learning. J Neurophysiol 95: 1812-1825, 2006.

Highstein SM, and Holstein GR. The anatomy of the vestibular nuclei. Prog Brain Res 151: 157-203, 2006.

Rabbitt RD, Breneman KD, King C, Yamauchi, A, Boyle R and Highstein SM. Dynamic displacement of normal and detached semicircular canal cupula.  J Assoc Res Otolaryngol.  Dec;10(4):497-509. PMID: 19513793.  PMCID: PMC2774407, 2009.

Boyle R, Rabbitt RD. and Highstein SM. Efferent Control of Hair Cell and Afferent Responses in the Semicircular Canals. In Press J. Neurophysiol. Sep;102(3):1513-25, PMID: 19571186. PMCID: PMC2746798, 2009.

Rabbitt RD, Boyle R and Highstein SM. Amplification by hair cells in the semicircular canals.  PNAS Feb 23; 107(8): 3864-9.  PMID 20133982, 2010.

Rajguru SM, Richter CP, Matic AI, Holstein GR, Highstein SM, Dittami GM and Rabbitt RD. Infrared photostimulation of the crista ampullaris. J. Physiology 589: 1283-1294. PMID 21242259 . Article featured in a Perspective:  I. S. Curthoys (2011)  A red thread as a guide in the vestibular labyrinth. J. Physiol. 589 (6) 1241.

Highstein SM, Holstein GR, Mann MA and Rabbitt RD. Evidence that Protons Act as Neurotransmitters at Vestibular Hair Cell Calyx Afferent Synapses.  PNAS. In Press, 2013.