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J. Christopher Holt, Ph.D.

J. Christopher Holt, Ph.D.

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Office (585) 273-3064

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About Me

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 ...
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

Faculty Appointments

Associate Professor - Department of Otolaryngology (SMD)

Credentials

Education

PhD | Tulane University Sch Medicine. Pharmacology and Toxicology. 1999

BS | Pembroke State Univ. Biology. 1991

MS | Northeast Louisiana University. Biology. 0

Awards

Advanced Predoctoral Fellowship. 1997 - 1999

James F. Ebert Award. 1989

J.P. Stevens Scholarship. 1989 - 1990

Chancellor's Scholar Program. 1986 - 1991

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 delivere...
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.

Publications

Journal Articles

Outer hair cells stir cochlear fluids.

Lee C, Shokrian M, Henry KS, Carney LH, Holt JC, Nam JH

eLife.. 2025 January 1613 Epub 01/16/2025.

is required to maintain supporting cell identity and vestibular function during maturation of the mammalian balance organs.

Heffer A, Lee C, Mayernik JP, Holt JC, Kiernan AE

The Journal of neuroscience : the official journal of the Society for Neuroscience.. 2025 January 8 Epub 01/08/2025.

Outer hair cells stir cochlear fluids.

Lee C, Shokrian M, Henry KS, Carney LH, Holt JC, Nam JH

bioRxiv : the preprint server for biology.. 2024 November 12 Epub 11/12/2024.

is required to maintain supporting cell identity and vestibular function during maturation of the mammalian balance organs.

Heffer A, Lee C, Holt JC, Kiernan AE

bioRxiv : the preprint server for biology.. 2024 June 21 Epub 06/21/2024.

Molecular and Functional Changes to Postsynaptic Cholinergic Signaling in the Vestibular Sensory Organs of Aging C57BL/6 Mice.

Poppi LA, Bigland MJ, Cresswell ET, Tabatabaee H, Lorincz D, Drury HR, Callister RJ, Holt JC, Lim R, Brichta AM, Smith DW

The journals of gerontology. Series A, Biological sciences and medical sciences.. 2023 June 178 (6):920-929. Epub 1900 01 01.

The mammalian efferent vestibular system utilizes cholinergic mechanisms to excite primary vestibular afferents.

Schneider GT, Lee C, Sinha AK, Jordan PM, Holt JC

Scientific reports.. 2021 January 1311 (1):1231. Epub 01/13/2021.

Characterizing the Access of Cholinergic Antagonists to Efferent Synapses in the Inner Ear.

Lee C, Sinha AK, Henry K, Walbaum AW, Crooks PA, Holt JC

Frontiers in neuroscience.. 2021 15 :754585. Epub 12/14/2021.

The Long and Winding Road-Vestibular Efferent Anatomy in Mice.

Lorincz D, Poppi LA, Holt JC, Drury HR, Lim R, Brichta AM

Frontiers in neural circuits.. 2021 15 :751850. Epub 01/28/2022.

Interactions between Passive and Active Vibrations in the Organ of Corti In Vitro.

Jabeen T, Holt JC, Becker JR, Nam JH

Biophysical journal.. 2020 July 21119 (2):314-325. Epub 06/17/2020.

A review of efferent cholinergic synaptic transmission in the vestibular periphery and its functional implications.

Poppi LA, Holt JC, Lim R, Brichta AM

Journal of neurophysiology.. 2020 February 1123 (2):608-629. Epub 12/04/2019.

ACh-induced hyperpolarization and decreased resistance in mammalian type II vestibular hair cells.

Poppi LA, Tabatabaee H, Drury HR, Jobling P, Callister RJ, Migliaccio AA, Jordan PM, Holt JC, Rabbitt RD, Lim R, Brichta AM

Journal of neurophysiology.. 2018 January 1119 (1):312-325. Epub 10/04/2017.

Loss of ?-Calcitonin Gene-Related Peptide (?CGRP) Reduces Otolith Activation Timing Dynamics and Impairs Balance.

Jones SM, Vijayakumar S, Dow SA, Holt JC, Jordan PM, Luebke AE

Frontiers in molecular neuroscience.. 2018 11 :289. Epub 08/24/2018.

Effect of M-current modulation on mammalian vestibular responses to transient head motion.

Lee C, Holt JC, Jones TA

Journal of neurophysiology.. 2017 December 1118 (6):2991-3006. Epub 08/30/2017.

Muscarinic Acetylcholine Receptors and M-Currents Underlie Efferent-Mediated Slow Excitation in Calyx-Bearing Vestibular Afferents.

Holt JC, Jordan PM, Lysakowski A, Shah A, Barsz K, Contini D

The Journal of neuroscience : the official journal of the Society for Neuroscience.. 2017 February 1537 (7):1873-1887. Epub 01/16/2017.

Confirming a Role for ?9nAChRs and SK Potassium Channels in Type II Hair Cells of the Turtle Posterior Crista.

Parks XX, Contini D, Jordan PM, Holt JC

Frontiers in cellular neuroscience.. 2017 11 :356. Epub 11/21/2017.

Maturation of suprathreshold auditory nerve activity involves cochlear CGRP-receptor complex formation.

Dickerson IM, Bussey-Gaborski R, Holt JC, Jordan PM, Luebke AE

Physiological reports.. 2016 July 4 (14)Epub 1900 01 01.

Efferent innervation of turtle semicircular canal cristae: comparisons with bird and mouse.

Jordan PM, Fettis M, Holt JC

The Journal of comparative neurology.. 2015 June 1523 (8):1258-80. Epub 03/25/2015.

Pharmacologically distinct nicotinic acetylcholine receptors drive efferent-mediated excitation in calyx-bearing vestibular afferents.

Holt JC, Kewin K, Jordan PM, Cameron P, Klapczynski M, McIntosh JM, Crooks PA, Dwoskin LP, Lysakowski A

The Journal of neuroscience : the official journal of the Society for Neuroscience.. 2015 February 2535 (8):3625-43. Epub 1900 01 01.

Loss of ?-calcitonin gene-related peptide (?CGRP) reduces the efficacy of the Vestibulo-ocular Reflex (VOR).

Luebke AE, Holt JC, Jordan PM, Wong YS, Caldwell JS, Cullen KE

The Journal of neuroscience : the official journal of the Society for Neuroscience.. 2014 July 3034 (31):10453-8. Epub 1900 01 01.

A review of synaptic mechanisms of vestibular efferent signaling in turtles: extrapolation to efferent actions in mammals.

Jordan PM, Parks XX, Contini D, Holt JC

Journal of vestibular research : equilibrium & orientation.. 2013 23 (3):161-75. Epub 1900 01 01.

Quantal and nonquantal transmission in calyx-bearing fibers of the turtle posterior crista.

Holt JC, Chatlani S, Lysakowski A, Goldberg JM

Journal of neurophysiology.. 2007 September 98 (3):1083-101. Epub 06/27/2007.

Mechanisms of efferent-mediated responses in the turtle posterior crista.

Holt JC, Lysakowski A, Goldberg JM

The Journal of neuroscience : the official journal of the Society for Neuroscience.. 2006 December 2026 (51):13180-93. Epub 1900 01 01.

Transmission between type II hair cells and bouton afferents in the turtle posterior crista.

Holt JC, Xue JT, Brichta AM, Goldberg JM

Journal of neurophysiology.. 2006 January 95 (1):428-52. Epub 09/21/2005.

A pharmacologically distinct nicotinic ACh receptor is found in a subset of frog semicircular canal hair cells.

Holt JC, Lioudyno M, Guth PS

Journal of neurophysiology.. 2003 September 90 (3):1526-36. Epub 1900 01 01.

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.

Lioudyno MI, Verbitsky M, Glowatzki E, Holt JC, Boulter J, Zadina JE, Elgoyhen AB, Guth PS

Molecular and cellular neurosciences.. 2002 August 20 (4):695-711. Epub 1900 01 01.

The effect of proteolytic enzymes on the alpha9-nicotinic receptor-mediated response in isolated frog vestibular hair cells.

Holt JC, Lioudyno M, Athas G, Garcia MM, Perin P, Guth PS

Hearing research.. 2001 February 152 (1-2):25-42. Epub 1900 01 01.

Morphine inhibits an alpha9-acetylcholine nicotinic receptor-mediated response by a mechanism which does not involve opioid receptors.

Lioudyno MI, Verbitsky M, Holt JC, Elgoyhen AB, Guth PS

Hearing research.. 2000 November 149 (1-2):167-77. Epub 1900 01 01.

A role for chloride in the hyperpolarizing effect of acetylcholine in isolated frog vestibular hair cells.

Holt JC, Pantoja AM, Athas GB, Guth PS

Hearing research.. 2000 August 146 (1-2):17-27. Epub 1900 01 01.

The metabotropic glutamate receptors of the vestibular organs.

Guth PS, Holt JC, Perin P, Athas G, Garcia M, Puri A, Zucca G, Botta L, Valli P

Hearing research.. 1998 November 125 (1-2):154-62. Epub 1900 01 01.

Mechanisms and effects of transepithelial polarization in the isolated semicircular canal.

Norris CH, Miller AJ, Perin P, Holt JC, Guth PS

Hearing research.. 1998 September 123 (1-2):31-40. Epub 1900 01 01.

A role for chloride in the suppressive effect of acetylcholine on afferent vestibular activity.

Pantoja AM, Holt JC, Guth PS

Hearing research.. 1997 October 112 (1-2):21-32. Epub 1900 01 01.

Ketorolac causes the release of methionine-enkephalin in rats.

Michel RE, Holt JC, Domer FR

Research communications in molecular pathology and

Books

Handbook of Auditory Research: Auditory and Vestibular Efferents (2011)

Chapter: Vestibular Efferents