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J. Christopher Holt, Ph.D.

Contact Information

Phone Numbers

Office: (585) 273-3064

Research Labs

Faculty Appointments

Biography

RESEARCH:

Cellular and Molecular Mechanisms of Synaptic Transmission in the Vestibular Periphery.

Many sensory systems are endowed with efferent feedback mechanisms that can modulate their primary input to the brain. That is, incoming information from a peripheral detector is delivered to a way station within the CNS which then modifies the output from that same detector. Everyday examples include the pupillary reflex to bright light entering the eyes, the contraction of middle ear muscles to loud sounds, or the recruitment of additional muscle fibers when first lifting a heavy object. Here, the function of the efferent loop is presumably to optimize or "tune" each sensory modality to its stimulus. Sensory information regarding the position and movement of the head are encoded by the vestibular system, which begins as a number of small detectors located within the inner ear. Like the preceding examples, the peripheral vestibular system is also endowed with a prominent efferent innervation. The functional role of this feedback system, however, is relatively unknown. We do know that when these efferent pathways are electrically stimulated, afferent output from vestibular endorgans is profoundly inhibited or excited, suggesting that vestibular efferents may be involved in both negative and positive feedback. If such efferent activity occurs under physiological conditions, it is almost certain to modify and transform vestibular information traveling to the CNS. Yet, very little information is available as to how and when these efferent actions ultimately impact the processing of vestibular information in an alert animal. Taking a reductionistic approach, my lab is addressing the function of the vestibular efferent system from three vantage points: (1) Identifying the receptor mechanisms by which different efferent responses are generated during activation of their pathways; (2) Characterizing how these efferent receptor mechanisms modulate afferent response properties by pairing afferent recordings during vestibular stimulation with activation of efferent pathways; and (3) Identification of efferent discharge patterns with direct, in vivo recordings from vestibular efferent neurons. Such knowledge is critical in evaluating efferent function in behaving animal models, one of our long term goals.

Professional Background

EDUCATION:

University of North Carolina at Pembroke BS 1986-1991 Biology, Chemistry
University of Louisiana at Monroe 1991-1994 Biology
Tulane University School of Medicine Ph.D. 1994-1999 Pharmacology
University of Chicago 2000-2005 Postdoctoral Training

POSITIONS AND EMPLOYMENT:

1991 – 1994 Graduate Assistant; Dept. of Biology, University of Louisiana at Monroe
1996 – 1999 Lab Instructor / Lecturer; Dept. of Pharmacology, Tulane University School of Medicine
2000 – 2005 Postdoctoral Fellow (2000-2003), Research Associate (2004), Instructor (2005); Advisor: Jay M. Goldberg, Ph.D. Department of Neurobiology, Pharmacology, and Physiology, University of Chicago
2005 – 2008 Assistant Professor, Department of Otolaryngology, University of Texas Medical Branch
2008 – Pres. Assistant Professor, Department of Otolaryngology, University of Rochester

HONORS AND AWARDS:

1989 James F. Ebert Award, University of North Carolina at Pembroke
1989-1990 J.P. Stevens Scholarship, University of North Carolina at Pembroke
1986-1991 Chancellor's Scholar Program, University of North Carolina at Pembroke
1997-1999 Pharmaceutical and Research Manufacturers of America (PhRMA), Advanced Predoctoral Fellowship

Research

RESEARCH:

Cellular and Molecular Mechanisms of Synaptic Transmission in the Vestibular Periphery.

Many sensory systems are endowed with efferent feedback mechanisms that can modulate their primary input to the brain. That is, incoming information from a peripheral detector is delivered to a way station within the CNS which then modifies the output from that same detector. Everyday examples include the pupillary reflex to bright light entering the eyes, the contraction of middle ear muscles to loud sounds, or the recruitment of additional muscle fibers when first lifting a heavy object. Here, the function of the efferent loop is presumably to optimize or "tune" each sensory modality to its stimulus. Sensory information regarding the position and movement of the head are encoded by the vestibular system, which begins as a number of small detectors located within the inner ear. Like the preceding examples, the peripheral vestibular system is also endowed with a prominent efferent innervation. The functional role of this feedback system, however, is relatively unknown. We do know that when these efferent pathways are electrically stimulated, afferent output from vestibular endorgans is profoundly inhibited or excited, suggesting that vestibular efferents may be involved in both negative and positive feedback. If such efferent activity occurs under physiological conditions, it is almost certain to modify and transform vestibular information traveling to the CNS. Yet, very little information is available as to how and when these efferent actions ultimately impact the processing of vestibular information in an alert animal. Taking a reductionistic approach, my lab is addressing the function of the vestibular efferent system from three vantage points: (1) Identifying the receptor mechanisms by which different efferent responses are generated during activation of their pathways; (2) Characterizing how these efferent receptor mechanisms modulate afferent response properties by pairing afferent recordings during vestibular stimulation with activation of efferent pathways; and (3) Identification of efferent discharge patterns with direct, in vivo recordings from vestibular efferent neurons. Such knowledge is critical in evaluating efferent function in behaving animal models, one of our long term goals.

AREA OF RESEARCH:

Sensory pharmacology with an emphasis on efferent and afferent neurotransmission in the vestibular periphery
Cholinergic mechanisms and systems
Glutamatergic mechanisms and systems

RECENT PUBLICATIONS:

Holt JC, Chatlani S, Lysakowski A, Goldberg JM. Quantal and Non-quantal Transmission in Calyx-Bearing Fibers of the Turtle Posterior Crista. J Neurophysiol. 98:1083-101, 2007.

Holt JC, Lysakowski A, Goldberg JM. Mechanisms of efferent-mediated responses in the turtle posterior crista. J Neurosci. 26:13180-93, 2006.

Holt JC, Xue JT, Brichta AM, Goldberg JM. Transmission between type II hair cells and bouton afferents in the turtle posterior crista. J Neurophysiol. 95: 428-452, 2006.

Holt JC, Lioudyno M, Guth PS. A pharmacologically distinct nicotinic ACh receptor is found in a subset of frog semicircular canal hair cells. J Neurophysiol. 90: 1526-36, 2003.

Lioudyno MI, Verbitsky M, Glowatzki E, Holt JC, Boulter J, Zadina JE, Elgoyhen AB, Guth PS. The alpha9/alpha10-containing nicotinic ACh receptor is directly modulated by opioid peptides, endomorphin-1, and dynorphin B, proposed efferent cotransmitters in the inner ear. Mol Cell Neurosci. 20: 695-711, 2002.

Holt JC, Lioudyno M, Athas GB, Garcia MM, Perin P, Guth PS. The effects of proteolytic enzymes on the alpha9-nicotinic receptor-mediated response in isolated frog vestibular hair cells. Hear Res. 152: 25-42, 2001.

Credentials

Education

1991
BS | Pembroke State Univ
Biology

1991-1994
MS | Northeast Louisiana University
Biology

1999
PhD | Tulane University Sch Medicine
Pharmacology and Toxicology

Awards

1997 - 1999
Advanced Predoctoral Fellowship
Sponsor: Pharmaceutical and Research Manufacturers of America (PhRMA)

1989 - 1990
J.P. Stevens Scholarship
Sponsor: University of North Carolina at Pembroke

1989
James F. Ebert Award
Sponsor: University of North Carolina at Pembroke

1986 - 1991
Chancellor's Scholar Program
Sponsor: University of North Carolina at Pembroke

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Publications

Journal Articles

2/25/2023
Poppi LA, Bigland MJ, Cresswell ET, Tabatabaee H, Lorincz D, Drury HR, Callister RJ, Holt JC, Lim R, Brichta AM, Smith DW. "Molecular and functional changes to postsynaptic cholinergic signaling in the vestibular sensory organs of aging C57BL/6 mice." The journals of gerontology. Series A, Biological sciences and medical sciences.. 2023 Feb 25; Epub 2023 Feb 25.

1/13/2021
Schneider GT, Lee C, Sinha AK, Jordan PM, Holt JC. "The mammalian efferent vestibular system utilizes cholinergic mechanisms to excite primary vestibular afferents." Scientific reports.. 2021 Jan 13; 11(1):1231. Epub 2021 Jan 13.

2021
Lee C, Sinha AK, Henry K, Walbaum AW, Crooks PA, Holt JC. "Characterizing the Access of Cholinergic Antagonists to Efferent Synapses in the Inner Ear." Frontiers in neuroscience.. 2021 15:754585. Epub 2021 Dec 14.

Books & Chapters

2011
Chapter Title: Vestibular Efferents
Book Title: Handbook of Auditory Research: Auditory and Vestibular Efferents
Author List: Holt JC: Lysakowski A: Goldberg JM
Edited By: Ryugo DK, Fay RR, Popper AN
Published By: Springer 2011

VIEW ALL PUBLICATIONS