Auditory Brain Stem Responses in the C57BL/6J Fragile X Syndrome-Knockout Mouse Model

Chawla, Amita; McCullagh, Elizabeth A.

doi:10.3389/fnint.2021.803483

Cited by 11 publications

(15 citation statements)

References 58 publications

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“…In fact, CF higher than 24 kHz were almost absent in Fmr1 -/-mouse IC (Figure 1D, right) despite being recorded in similar if not deeper depth (Supplementary Figure 1 and Table 1). Whether a loss of FMRP impacts tonotopic representation in the IC, as previously shown in the MNTB and indirectly in the IC (Strumbos et al, 2010;McCullagh et al, 2017;Chawla and McCullagh, 2022), needs to be confirmed using different methods.…”

Section: Resultsmentioning

confidence: 95%

“…Genotype specific changes in threshold, firing rate, frequency tuning and binaural response properties in inferior colliculus neurons are similar to auditory brainstem neurons In contrast to many previous studies we found a trend for a decrease in response thresholds that reached significance for transient firing neurons. All studies that reported increased thresholds used auditory brainstem responses (ABRs) which measure population activity including synaptic field potentials for threshold determination (Rotschafer et al, 2015;McCullagh et al, 2020b;Chawla and McCullagh, 2022). These thresholds always take into account the total number of neurons being activated and may therefore differ, when compared to thresholds obtained by recordings of single neuron action potentials.…”

Section: Discussionmentioning

confidence: 99%

“…The unequal sex distribution with considerably less females originates from the breeding scheme proposed by the supplier. Since we did not observe sex differences in response patterns in auditory brainstem neurons in a previous study (Garcia-Pino et al, 2017), we did not correct for this discrepancy during the experiments what should probably be now taken into account given the recent publications showing otherwise (McCullagh et al, 2020a;Chawla and McCullagh, 2022). Statistical analyses were conducted with Matlab (RRID:SCR_001622).…”

Section: Experimental Design and Statistical Analysismentioning

confidence: 99%

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Absence of the Fragile X messenger ribonucleoprotein alters response patterns to sounds in the auditory midbrain

2022

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Among the different autism spectrum disorders, Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. Sensory and especially auditory hypersensitivity is a key symptom in patients, which is well mimicked in the Fmr1 -/mouse model. However, the physiological mechanisms underlying FXS's acoustic hypersensitivity in particular remain poorly understood. Here, we categorized spike response patterns to pure tones of different frequencies and intensities from neurons in the inferior colliculus (IC), a central integrator in the ascending auditory pathway. Based on this categorization we analyzed differences in response patterns between IC neurons of wild-type (WT) and Fmr1 -/mice. Our results report broadening of frequency tuning, an increased firing in response to monaural as well as binaural stimuli, an altered balance of excitation-inhibition, and reduced response latencies, all expected features of acoustic hypersensitivity. Furthermore, we noticed that all neuronal response types in Fmr1 -/mice displayed enhanced offset-rebound activity outside their excitatory frequency response area. These results provide evidence that the loss of Fmr1 not only increases spike responses in IC neurons similar to auditory brainstem neurons, but also changes response patterns such as offset spiking. One can speculate this to be an underlying aspect of the receptive language problems associated with Fragile X syndrome.

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Section: Resultsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Experimental Design and Statistical Analysismentioning

confidence: 99%

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Absence of the Fragile X messenger ribonucleoprotein alters response patterns to sounds in the auditory midbrain

2022

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“…These results also informed the PRF parameters used in later motor response trials. The amplitudes of skull vibrations across each PRF were then adjusted based on the auditory sensitivity of the mouse to that frequency, as taken from Chawla and McCullagh (2022). This resulted in a second response curve indicating the audibility of each PRF.…”

Section: Experimental Executionmentioning

confidence: 99%

Investigating the impact of skull vibrations on motor responses to focused ultrasound neuromodulation in small rodents and methods to mitigate them

Hesselink,

Krasnichuk,

Benaceur

et al. 2023

Phys. Med. Biol.

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Objective: Focused ultrasound (FUS) neuromodulation non-invasively alters brain activity, likely via acoustic radiation force (ARF) with dynamics of the pulse repetition frequency (PRF). PRF impacts neuromodulation as well as indirect auditory activation, a confound linked to skull vibrations. This study aimed to minimize these vibrations, by adjusting and randomizing PRF, and determine their impact on FUS-induced motor activity. We hypothesized that: the skull would vibrate most at a specific PRF; randomizing PRF would reduce skull vibrations without affecting motor responses; and FUS would yield motor activity while actuator-induced skull vibrations would not. Approach: Three objectives were studied in parallel using C57Bl/6 mice (n = number of mice used per objective). First, skull vibration amplitude, measured as a percentage of maximum amplitude per treatment, was recorded via contact microphone over a range of PRFs to assess the PRF-dependency of skull vibrations (n = 19). Vibrations were then compared between random and fixed PRFs (n = 15). Lastly, motor responses were compared between fixed 1.5 kHz PRF FUS, random PRF FUS, air-puff stimulation, sham stimulation, and vibration induction via piezoelectric actuator (n = 30). Main Results: The study found amplitude peaked at 1.51 kHz (88.1 ± 11.5%), significantly higher than at 0.54 kHz (75.5 ± 15.1%; p = 0.0149). Random PRF reduced amplitude by 4.2% (p = 0.0181). Motor response rates to actuator-induced skull vibrations at the PRF (5.73 ± 6.96%) and its third harmonic (22.9 ± 22.7%) were not significantly different than sham (14.1 ± 11.6%), but lower than FUS (70.2 ± 16.3%; p < 0.0001). Significance: Based on these results, PRF near 0.5 kHz may best avoid skull vibrations, while random PRF could be utilized to slightly reduce vibration amplitude. The results also suggested that skull vibrations likely do not significantly impact motor responses to FUS neuromodulation.

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“…ABR measurements and analysis methods are described in previous publications [24][25][26][27]. Naked mole-rats were anaesthetized with a mixture of ketamine-xylazine (100 mg kg −1 , 10 mg kg −1 , respectively) administered via intraperitoneal injections.…”

Section: (B) Auditory Brainstem Response Measurementsmentioning

confidence: 99%

Auditory brainstem development of naked mole-rats (Heterocephalus glaber)

et al. 2022

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Life underground often leads to animals having specialized auditory systems to accommodate the constraints of acoustic transmission in tunnels. Despite living underground, naked mole-rats use a highly vocal communication system, implying that they rely on central auditory processing. However, little is known about these animals' central auditory system, and whether it follows a similar developmental time course as other rodents. Naked mole-rats show slowed development in the hippocampus suggesting they have altered brain development compared to other rodents. Here, we measured morphological characteristics and voltage-gated potassium channel K v 3.3 expression and protein levels at different key developmental time points (postnatal days 9, 14, 21 and adulthood) to determine whether the auditory brainstem (lateral superior olive and medial nucleus of the trapezoid body) develops similarly to two common auditory rodent model species: gerbils and mice. Additionally, we measured the hearing onset of naked mole-rats using auditory brainstem response recordings at the same developmental timepoints. In contrast with other work in naked mole-rats showing that they are highly divergent in many aspects of their physiology, we show that naked mole-rats have a similar hearing onset, between postnatal day (P) 9 and P14, to many other rodents. On the other hand, we show some developmental differences, such as a unique morphology and K v 3.3 protein levels in the brainstem.

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Auditory Brain Stem Responses in the C57BL/6J Fragile X Syndrome-Knockout Mouse Model

Cited by 11 publications

References 58 publications

Absence of the Fragile X messenger ribonucleoprotein alters response patterns to sounds in the auditory midbrain

Absence of the Fragile X messenger ribonucleoprotein alters response patterns to sounds in the auditory midbrain

Investigating the impact of skull vibrations on motor responses to focused ultrasound neuromodulation in small rodents and methods to mitigate them

Auditory brainstem development of naked mole-rats (Heterocephalus glaber)

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