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Article: Depolarization shift in the resting membrane potential of inferior colliculus neurons explains their hyperactivity induced by an acoustic trauma.

Hsiao, Chun-Jen / Galazyuk, Alexander V

2023 Volume 17, Page(s) 1258349

Abstract: Introduction: Neuronal hyperactivity has been associated with many brain diseases. In the auditory system, hyperactivity has been linked to hyperacusis and tinnitus. Previous research demonstrated the development of hyperactivity in inferior colliculus ( ...

Abstract	Introduction: Neuronal hyperactivity has been associated with many brain diseases. In the auditory system, hyperactivity has been linked to hyperacusis and tinnitus. Previous research demonstrated the development of hyperactivity in inferior colliculus (IC) neurons after sound overexposure, but the underlying mechanism of this hyperactivity remains unclear. The main goal of this study was to determine the mechanism of this hyperactivity. Methods: Experiments were performed on CBA/CaJ mice in a restrained, unanesthetized condition using intracellular recordings with sharp microelectrodes. Recordings were obtained from control (unexposed) and unilaterally sound overexposed groups of mice. Results: Our data suggest that sound exposure-induced hyperactivity was due to a depolarizing shift of the resting membrane potential (RMP) in the hyperactive neurons. The half width of action potentials in these neurons was also decreased after sound exposure. Surprisingly, we also found an RMP gradient in which neurons have more hyperpolarized RMPs with increasing depth in the IC. This gradient was altered in the overexposed animals.
Language	English
Publishing date	2023-09-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2023.1258349
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Article ; Online: Intracellular recordings reveal integrative function of the basolateral amygdala in acoustic communication.

Voytenko, Sergiy / Shanbhag, Sharad / Wenstrup, Jeffrey / Galazyuk, Alexander

Journal of neurophysiology

2023 Volume 129, Issue 6, Page(s) 1334–1343

Abstract: The amygdala, a brain center of emotional expression, contributes to appropriate behavior responses during acoustic communication. In support of that role, the basolateral amygdala (BLA) analyzes the meaning of vocalizations through the integration of ... ...

Abstract	The amygdala, a brain center of emotional expression, contributes to appropriate behavior responses during acoustic communication. In support of that role, the basolateral amygdala (BLA) analyzes the meaning of vocalizations through the integration of multiple acoustic inputs with information from other senses and an animal's internal state. The mechanisms underlying this integration are poorly understood. This study focuses on the integration of vocalization-related inputs to the BLA from auditory centers during this processing. We used intracellular recordings of BLA neurons in unanesthetized big brown bats that rely heavily on a complex vocal repertoire during social interactions. Postsynaptic and spiking responses of BLA neurons were recorded to three vocal sequences that are closely related to distinct behaviors (appeasement, low-level aggression, and high-level aggression) and have different emotional valence. Our novel findings are that most BLA neurons showed postsynaptic responses to one or more vocalizations (31 of 46) but that many fewer neurons showed spiking responses (8 of 46). The spiking responses were more selective than postsynaptic potential (PSP) responses. Furthermore, vocal stimuli associated with either positive or negative valence were similarly effective in eliciting excitatory postsynaptic potentials (EPSPs), inhibitory postsynaptic potentials (IPSPs), and spiking responses. This indicates that BLA neurons process both positive- and negative-valence vocal stimuli. The greater selectivity of spiking responses than PSP responses suggests an integrative role for processing within the BLA to enhance response specificity in acoustic communication.
MeSH term(s)	Animals ; Basolateral Nuclear Complex ; Neurons/physiology ; Amygdala/physiology ; Vocalization, Animal/physiology ; Acoustics
Language	English
Publishing date	2023-04-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00103.2023
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Article: Effect of Unilateral Acoustic Trauma on Neuronal Firing Activity in the Inferior Colliculus of Mice.

Hsiao, Chun-Jen / Galazyuk, Alexander V

Frontiers in synaptic neuroscience

2021 Volume 13, Page(s) 684141

Abstract: Neural hyperactivity induced by sound exposure often correlates with the development of hyperacusis and/or tinnitus. In laboratory animals, hyperactivity is typically induced by unilateral sound exposure to preserve one ear for further testing of hearing ...

Abstract	Neural hyperactivity induced by sound exposure often correlates with the development of hyperacusis and/or tinnitus. In laboratory animals, hyperactivity is typically induced by unilateral sound exposure to preserve one ear for further testing of hearing performance. Most ascending fibers in the auditory system cross into the superior olivary complex and then ascend contralaterally. Therefore, unilateral exposure should be expected to mostly affect the contralateral side above the auditory brain stem. On the other hand, it is well known that a significant number of neurons have crossing fibers at every level of the auditory pathway, which may spread the effect of unilateral exposure onto the ipsilateral side. Here we demonstrate that unilateral sound exposure causes development of hyperactivity in both the contra and ipsilateral inferior colliculus in mice. We found that both the spontaneous firing rate and bursting activity were increased significantly compared to unexposed mice. The neurons with characteristic frequencies at or above the center frequency of exposure showed the greatest increase. Surprisingly, this increase was more pronounced in the ipsilateral inferior colliculus.
Language	English
Publishing date	2021-06-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2592086-8
ISSN	1663-3563
ISSN	1663-3563
DOI	10.3389/fnsyn.2021.684141
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Article ; Online: Animal Models of Tinnitus: A Review.

Galazyuk, Alexander / Brozoski, Thomas J

Otolaryngologic clinics of North America

2020 Volume 53, Issue 4, Page(s) 469–480

Abstract: Animal models have significantly contributed to understanding the pathophysiology of chronic subjective tinnitus. They are useful because they control etiology, which in humans is heterogeneous; employ random group assignment; and often use methods not ... ...

Abstract	Animal models have significantly contributed to understanding the pathophysiology of chronic subjective tinnitus. They are useful because they control etiology, which in humans is heterogeneous; employ random group assignment; and often use methods not permissible in human studies. Animal models can be broadly categorized as either operant or reflexive, based on methodology. Operant methods use variants of established psychophysical procedures to reveal what an animal hears. Reflexive methods do the same using elicited behavior, for example, the acoustic startle reflex. All methods contrast the absence of sound and presence of sound, because tinnitus cannot by definition be perceived as silence.
MeSH term(s)	Acoustic Stimulation ; Animals ; Behavior, Animal ; Disease Models, Animal ; Hearing ; Hearing Loss ; Humans ; Reflex ; Reflex, Startle ; Reproducibility of Results ; Sound ; Tinnitus/physiopathology
Language	English
Publishing date	2020-04-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	417489-6
ISSN	1557-8259 ; 0030-6665
ISSN (online)	1557-8259
ISSN	0030-6665
DOI	10.1016/j.otc.2020.03.001
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Article: Variable Effects of Acoustic Trauma on Behavioral and Neural Correlates of Tinnitus In Individual Animals.

Longenecker, Ryan J / Galazyuk, Alexander V

Frontiers in behavioral neuroscience

2016 Volume 10, Page(s) 207

Abstract: The etiology of tinnitus is known to be diverse in the human population. An appropriate animal model of tinnitus should incorporate this pathological diversity. Previous studies evaluating the effect of acoustic over exposure (AOE) have found that ... ...

Abstract	The etiology of tinnitus is known to be diverse in the human population. An appropriate animal model of tinnitus should incorporate this pathological diversity. Previous studies evaluating the effect of acoustic over exposure (AOE) have found that animals typically display increased spontaneous firing rates and bursting activity of auditory neurons, which often has been linked to behavioral evidence of tinnitus. However, only a subset of studies directly associated these neural correlates to individual animals. Furthermore, the vast majority of tinnitus studies were conducted on anesthetized animals. The goal of this study was to test for a possible relationship between tinnitus, hearing loss, hyperactivity and bursting activity in the auditory system of individual unanesthetized animals following AOE. Sixteen mice were unilaterally exposed to 116 dB SPL narrowband noise (centered at 12.5 kHz) for 1 h under ketamine/xylazine anesthesia. Gap-induced prepulse inhibition of the acoustic startle reflex (GPIAS) was used to assess behavioral evidence of tinnitus whereas hearing performance was evaluated by measurements of auditory brainstem response (ABR) thresholds and prepulse inhibition PPI audiometry. Following behavioral assessments, single neuron firing activity was recorded from the inferior colliculus (IC) of four awake animals and compared to recordings from four unexposed controls. We found that AOE increased spontaneous activity in all mice tested, independently of tinnitus behavior or severity of threshold shifts. Bursting activity did not increase in two animals identified as tinnitus positive (T+), but did so in a tinnitus negative (T-) animal with severe hearing loss (SHL). Hyperactivity does not appear to be a reliable biomarker of tinnitus. Our data suggest that multidisciplinary assessments on individual animals following AOE could offer a powerful experimental tool to investigate mechanisms of tinnitus.
Language	English
Publishing date	2016-10-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452960-6
ISSN	1662-5153
ISSN	1662-5153
DOI	10.3389/fnbeh.2016.00207
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Article: Gap-Prepulse Inhibition of the Acoustic Startle Reflex (GPIAS) for Tinnitus Assessment: Current Status and Future Directions.

Galazyuk, Alexander / Hébert, Sylvie

Frontiers in neurology

2015 Volume 6, Page(s) 88

Abstract: The progress in the field of tinnitus largely depends on the development of a reliable tinnitus animal model. Recently, a new method based on the acoustic startle reflex modification was introduced for tinnitus screening in laboratory animals. This ... ...

Abstract	The progress in the field of tinnitus largely depends on the development of a reliable tinnitus animal model. Recently, a new method based on the acoustic startle reflex modification was introduced for tinnitus screening in laboratory animals. This method was enthusiastically adopted and now widely used by many scientists in the field due to its seeming simplicity and a number of advantages over the other methods of tinnitus assessment. Furthermore, this method opened an opportunity for tinnitus assessment in humans as well. Unfortunately, multiple modifications of data collection and interpretation implemented in different labs make comparisons across studies very difficult. In addition, recent animal and human studies have challenged the original "filling-in" interpretation of the paradigm. Here, we review the current literature to emphasize on the commonalities and differences in data collection and interpretation across laboratories that are using this method for tinnitus assessment. We also propose future research directions that could be taken in order to establish whether or not this method is warranted as an indicator of the presence of tinnitus.
Language	English
Publishing date	2015-04-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2015.00088
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Article ; Online: Group II Metabotropic Glutamate Receptors Modulate Sound Evoked and Spontaneous Activity in the Mouse Inferior Colliculus.

Kristaponyte, Inga / Beebe, Nichole L / Young, Jesse W / Shanbhag, Sharad J / Schofield, Brett R / Galazyuk, Alexander V

eNeuro

2021 Volume 8, Issue 1

Abstract: Little is known about the functions of Group II metabotropic glutamate receptors (mGluRs2/3) in the inferior colliculus (IC), a midbrain structure that is a major integration region of the central auditory system. We investigated how these receptors ... ...

Abstract	Little is known about the functions of Group II metabotropic glutamate receptors (mGluRs2/3) in the inferior colliculus (IC), a midbrain structure that is a major integration region of the central auditory system. We investigated how these receptors modulate sound-evoked and spontaneous firing in the mouse IC
MeSH term(s)	Animals ; Inferior Colliculi ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Receptors, Metabotropic Glutamate/genetics ; Sound
Chemical Substances	Receptors, Metabotropic Glutamate
Language	English
Publishing date	2021-01-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2800598-3
ISSN	2373-2822 ; 2373-2822
ISSN (online)	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0328-20.2020
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Article ; Online: Development of tinnitus in CBA/CaJ mice following sound exposure.

Longenecker, Ryan J / Galazyuk, Alexander V

Journal of the Association for Research in Otolaryngology : JARO

2011 Volume 12, Issue 5, Page(s) 647–658

Abstract: Tinnitus, the perception of a sound without an external acoustic source, is a complex perceptual phenomenon affecting the quality of life in 17% of the adult population. Despite its ubiquity and morbidity, the pathophysiology of tinnitus is a work in ... ...

Abstract	Tinnitus, the perception of a sound without an external acoustic source, is a complex perceptual phenomenon affecting the quality of life in 17% of the adult population. Despite its ubiquity and morbidity, the pathophysiology of tinnitus is a work in progress, and there is no generally accepted cure or treatment. Development of a reliable common animal model is crucial for tinnitus research and may advance this field. The goal of this study was to develop a tinnitus mouse model. Tinnitus was induced in an experimental group of mice by an exposure to a loud (116 dB sound pressure level (SPL)) narrow band noise (one octave, centered at 16 kHz) during 1 h under anesthesia. The tinnitus was then assessed behaviorally by measuring gap induced suppression of the acoustic startle reflex. We found that a vast majority of the sound-exposed mice (86%) developed behavioral signs of tinnitus. This was a complex, long lasting, and dynamic process. On the day following exposure, all mice demonstrated signs of acute tinnitus over the entire range of sound frequencies used for testing (10-31 kHz). However, 2-3 months later, a behavioral evidence of tinnitus was evident only at a narrow frequency range (20-31 kHz) representing a presumed chronic condition. Extracellular recordings confirmed a significantly higher rate of spontaneous activity in inferior colliculus neurons in sound-exposed compared to control mice. Surprisingly, unilateral sound exposure suppresses startle responses in mice and they remained suppressed even 3 months post-exposure, whereas auditory brainstem response thresholds were completely recovered during 2 months following exposure. In summary, behavioral evidence of tinnitus can be reliably developed in mice by sound exposure, and tinnitus induction can be assessed by quantifying prepulse inhibition of the acoustic startle reflex.
MeSH term(s)	Animals ; Evoked Potentials, Auditory, Brain Stem ; Mice ; Mice, Inbred CBA ; Noise/adverse effects ; Reflex ; Reflex, Startle ; Tinnitus/etiology ; Tinnitus/physiopathology
Language	English
Publishing date	2011-06-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2021417-0
ISSN	1438-7573 ; 1525-3961
ISSN (online)	1438-7573
ISSN	1525-3961
DOI	10.1007/s10162-011-0276-1
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Article ; Online: Generation of a ChAT

Beebe, Nichole L / Sowick, Colleen S / Kristaponyte, Inga / Galazyuk, Alexander V / Vetter, Douglas E / Cox, Brandon C / Schofield, Brett R

Hearing research

2020 Volume 388, Page(s) 107896

Abstract: The development of knockin mice with Cre recombinase expressed under the control of the promoter for choline acetyltransferase (ChAT) has allowed experimental manipulation of cholinergic circuits. However, currently available ... ...

Abstract	The development of knockin mice with Cre recombinase expressed under the control of the promoter for choline acetyltransferase (ChAT) has allowed experimental manipulation of cholinergic circuits. However, currently available ChAT
Language	English
Publishing date	2020-01-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	282629-x
ISSN	1878-5891 ; 0378-5955
ISSN (online)	1878-5891
ISSN	0378-5955
DOI	10.1016/j.heares.2020.107896
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Article ; Online: Addressing variability in the acoustic startle reflex for accurate gap detection assessment.

Longenecker, Ryan J / Kristaponyte, Inga / Nelson, Gregg L / Young, Jesse W / Galazyuk, Alexander V

Hearing research

2018 Volume 363, Page(s) 119–135

Abstract: The acoustic startle reflex (ASR) is subject to substantial variability. This inherent variability consequently shapes the conclusions drawn from gap-induced prepulse inhibition of the acoustic startle reflex (GPIAS) assessments. Recent studies have cast ...

Abstract	The acoustic startle reflex (ASR) is subject to substantial variability. This inherent variability consequently shapes the conclusions drawn from gap-induced prepulse inhibition of the acoustic startle reflex (GPIAS) assessments. Recent studies have cast doubt as to the efficacy of this methodology as it pertains to tinnitus assessment, partially, due to variability in and between data sets. The goal of this study was to examine the variance associated with several common data collection variables and data analyses with the aim to improve GPIAS reliability. To study this the GPIAS tests were conducted in adult male and female CBA/CaJ mice. Factors such as inter-trial interval, circadian rhythm, sex differences, and sensory adaptation were each evaluated. We then examined various data analysis factors which influence GPIAS assessment. Gap-induced facilitation, data processing options, and assessments of tinnitus were studied. We found that the startle reflex is highly variable in CBA/CaJ mice, but this can be minimized by certain data collection factors. We also found that careful consideration of temporal fluctuations of the ASR and controlling for facilitation can lead to more accurate GPIAS results. This study provides a guide for reducing variance in the GPIAS methodology - thereby improving the diagnostic power of the test.
MeSH term(s)	Acoustic Stimulation ; Adaptation, Psychological ; Animals ; Auditory Pathways/physiopathology ; Auditory Perception ; Behavior, Animal ; Circadian Rhythm ; Disease Models, Animal ; Female ; Hearing Tests/methods ; Male ; Mice, Inbred CBA ; Predictive Value of Tests ; Prepulse Inhibition ; Reflex, Startle ; Reproducibility of Results ; Sex Factors ; Signal Detection, Psychological ; Tinnitus/diagnosis ; Tinnitus/physiopathology ; Tinnitus/psychology
Language	English
Publishing date	2018-03-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	282629-x
ISSN	1878-5891 ; 0378-5955
ISSN (online)	1878-5891
ISSN	0378-5955
DOI	10.1016/j.heares.2018.03.013
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