Mouse Auditory Brainstem Response Testing

Akil, Omar; Oursler, A E; Fan, Kevin; Lustig, Lawrence R.

doi:10.21769/bioprotoc.1768

Cited by 38 publications

(22 citation statements)

References 5 publications

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“…The ABR is characterized by a series of electrical waves, labeled as waves I to V (Jewett and Williston, 1971;Song et al, 2006), representing the progressive transfer of the auditory signal from the periphery to the CNS. Wave I represents the summated response from the spiral ganglion and auditory nerve, while waves II to V represent responses from the ascending auditory pathway (Akil et al, 2016).…”

Section: Loss Of Fmrp Alters Central Processing Of Auditory Informationmentioning

confidence: 99%

Modulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice

El-Hassar

Song

Tan³

et al. 2019

J. Neurosci.

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Fragile X syndrome (FXS) is characterized by hypersensitivity to sensory stimuli, including environmental sounds. We compared the auditory brainstem response (ABR) recorded in vivo in mice lacking the gene (Fmr1 ؊/y ) for fragile X mental retardation protein (FMRP) with that in wild-type animals. We found that ABR wave I, which represents input from the auditory nerve, is reduced in Fmr1 ؊/y animals, but only at high sound levels. In contrast, wave IV, which represents the activity of auditory brainstem nuclei is enhanced at all sound levels, suggesting that loss of FMRP alters the central processing of auditory signals. Current-clamp recordings of neurons in the medial nucleus of the trapezoid body in the auditory brainstem revealed that, in contrast to neurons from wild-type animals, sustained depolarization triggers repetitive firing rather than a single action potential. In voltage-clamp recordings, K ϩ currents that activate at positive potentials ("high-threshold" K ϩ currents), which are required for high-frequency firing and are carried primarily by Kv3.1 channels, are elevated in Fmr1 ؊/y mice, while K ϩ currents that activate near the resting potential and inhibit repetitive firing are reduced. We therefore tested the effects of AUT2 [((4-({5-[(4R)-4-ethyl-2,5-dioxo-1-imidazolidinyl]-2-pyridinyl}oxy)-2-(1-methylethyl) benzonitrile], a compound that modulates Kv3.1 channels. AUT2 reduced the high-threshold K ϩ current and increased the low-threshold K ϩ currents in neurons from Fmr1 ؊/y animals by shifting the activation of the high-threshold current to more negative potentials. This reduced the firing rate and, in vivo, restored wave IV of the ABR. Our results from animals of both sexes suggest that the modulation of the Kv3.1 channel may have potential for the treatment of sensory hypersensitivity in patients with FXS. Key words: auditory brainstem response; AUT2; fragile X; high-and low-threshold potassium channels; medial nucleus of the trapezoid body; potassium channelsSignificance Statement mRNA encoding the Kv3.1 potassium channel was one of the first described targets of the fragile X mental retardation protein (FMRP). Fragile X syndrome is caused by loss of FMRP and, in humans and mice, causes hypersensitivity to auditory stimuli. We found that components of the auditory brain response (ABR) corresponding to auditory brainstem activity are enhanced in mice lacking FMRP. This is accompanied by hyperexcitability and altered potassium currents in auditory brainstem neurons. Treatment with a drug that alters the voltage dependence of Kv3.1 channels normalizes the imbalance of potassium currents, as well as ABR responses in vivo, suggesting that such compounds may be effective in treating some symptoms of fragile X syndrome.

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Section: Loss Of Fmrp Alters Central Processing Of Auditory Informationmentioning

confidence: 99%

Modulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice

El-Hassar

Song

Tan³

et al. 2019

J. Neurosci.

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“…ABR tests were performed on rats to determine the hearing threshold of rats before and after chemical deafening. Rodents were sedated under isoflurane (2%), 2 pairs of gold cup electrodes (Model 019-772500, Natus Medical Inc., Pleasanton, CA, USA) filled with EEG conductive paste (Ten20, Weaver and Company, Aurora, CO, USA) were applied to the rodent skull to record bilateral ABR (Akil et al, 2016). Each pair of electrodes consists of one reference electrode at the forehead immediately below the left or right eye, and on the ipsilateral side, a recording electrode at the base of the ear.…”

Section: Auditory Brainstem Response (Abr) Testmentioning

confidence: 99%

Intrinsic Cell-type Selectivity and Inter-neuronal Connectivity Alteration by Transcranial Focused Ultrasound

Kang

Niu²,

Krook-Magnuson

et al. 2019

Preprint

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Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We investigate the effect of tFUS stimulation on different neuron types and synaptic connectivity in in vivo anesthetized rodent brains.Single units were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes, further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. For the first time, we show that excitatory neurons are significantly less responsive to low ultrasound pulse repetition frequencies (UPRFs), whereas the spike rates of inhibitory neurons do not change significantly across all UPRF levels. Our results suggest that we can preferentially target specific neuron types noninvasively by altering the tFUS UPRF. We also report in vivo observation of long-term synaptic connectivity changes induced by noninvasive tFUS in rats. This finding suggests tFUS can be used to encode temporally dependent stimulation paradigms into neural circuits and non-invasively elicit long-term changes in synaptic connectivity.

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“…oABRs were recorded using needle electrodes placed subdermally near the pinna, the vertex, and on the back, 49 at varying light intensities, with 210-420 pulses averaged at each light intensity. Acoustic auditory brainstem responses were recorded in response 16-kHz tone pip stimuli (30 pips/s, averaged to a total of 512 pulses at each decibel [dB] level, 0-80 dB, with a step size of 10 dB).…”

Section: Auditory Neurophysiologymentioning

confidence: 99%

Ancestral Adeno-Associated Virus Vector Delivery of Opsins to Spiral Ganglion Neurons: Implications for Optogenetic Cochlear Implants

et al. 2018

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Optogenetics is a transformative technology based on light-sensitive microbial proteins, known as opsins, that enable precise modulation of neuronal activity with pulsed radiant energy. Optogenetics has been proposed as a means to improve auditory implant outcomes by reducing channel interaction and increasing electrode density, but the introduction of opsins into cochlear spiral ganglion neurons (SGNs) in vivo has been challenging. Here we test opsin delivery using a synthetically developed ancestral adeno-associated virus (AAV) vector called Anc80L65. Wild-type C57BL/6 mouse pups were injected via the round window of cochlea with Anc80L65 carrying opsin Chronos under the control of a CAG promoter. Following an incubation of 6-22 weeks, pulsed blue light was delivered to cochlear SGNs via a cochleosotomy approach and flexible optical fiber. Optically evoked auditory brainstem responses (oABRs) and multiunit activity in inferior colliculus (IC) were observed. Post-experiment cochlear histology demonstrated opsin expression in SGNs (mean = 74%), with an even distribution of opsin along the cochlear basal/apical gradient. This study is the first to describe robust SGN transduction, opsin expression, and optically evoked auditory electrophysiology in neonatal mice. Ultimately, this work may provide the basis for a new generation of cochlear implant based on light.

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Mouse Auditory Brainstem Response Testing

Cited by 38 publications

References 5 publications

Modulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice

Modulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice

Intrinsic Cell-type Selectivity and Inter-neuronal Connectivity Alteration by Transcranial Focused Ultrasound

Ancestral Adeno-Associated Virus Vector Delivery of Opsins to Spiral Ganglion Neurons: Implications for Optogenetic Cochlear Implants

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