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An Overrepresentation of High Frequencies in the Mouse Inferior Colliculus Supports the Processing of Ultrasonic Vocalizations.

Garcia-Lazaro JA, Shepard KN, Miranda JA, Liu RC, Lesica NA - PLoS ONE (2015)

Bottom Line: Auditory brainstem response measurements suggested stronger responses in the midbrain relative to the periphery for frequencies higher than 32 kHz.This result was confirmed by single- and multi-unit recordings showing that high ultrasonic frequency tones and vocalizations elicited responses from only a small fraction of cells in the periphery, while a much larger fraction of cells responded in the inferior colliculus.These results suggest that the processing of communication calls in mice is supported by a specialization of the auditory system for high frequencies that emerges at central stations of the auditory pathway.

View Article: PubMed Central - PubMed

Affiliation: Ear Institute, University College London, 332 Grays Inn Road, London, WC1X 8EE, United Kingdom.

ABSTRACT
Mice are of paramount importance in biomedical research and their vocalizations are a subject of interest for researchers across a wide range of health-related disciplines due to their increasingly important value as a phenotyping tool in models of neural, speech and language disorders. However, the mechanisms underlying the auditory processing of vocalizations in mice are not well understood. The mouse audiogram shows a peak in sensitivity at frequencies between 15-25 kHz, but weaker sensitivity for the higher ultrasonic frequencies at which they typically vocalize. To investigate the auditory processing of vocalizations in mice, we measured evoked potential, single-unit, and multi-unit responses to tones and vocalizations at three different stages along the auditory pathway: the auditory nerve and the cochlear nucleus in the periphery, and the inferior colliculus in the midbrain. Auditory brainstem response measurements suggested stronger responses in the midbrain relative to the periphery for frequencies higher than 32 kHz. This result was confirmed by single- and multi-unit recordings showing that high ultrasonic frequency tones and vocalizations elicited responses from only a small fraction of cells in the periphery, while a much larger fraction of cells responded in the inferior colliculus. These results suggest that the processing of communication calls in mice is supported by a specialization of the auditory system for high frequencies that emerges at central stations of the auditory pathway.

No MeSH data available.


Related in: MedlinePlus

Auditory brainstem responses to click and tone stimuli.(A) ABRs recorded from one CBA/CaJ mouse in response to clicks of increasing intensity (individual traces from bottom to top). The star on the y-axis represents the threshold stimulus intensity. The different ABR peaks are labeled using roman numerals. (B) ABRs recorded from one CBA/CaJ mouse in response to pure-tone pips of increasing frequency (individual panels from bottom to top). Each panel shows the mean response (in color) averaged over 500 repeats. The black stippled line in each panel shows the mean response (± standard error) averaged over a population of 5 animals. The shaded areas in light green and pink indicate the timing of waves I and V respectively. (C) Amplitude of wave I vs. wave V at each of the frequencies we tested. Open circles represent the data obtained from individual animals. The lines join the mean values across different frequencies.
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pone.0133251.g001: Auditory brainstem responses to click and tone stimuli.(A) ABRs recorded from one CBA/CaJ mouse in response to clicks of increasing intensity (individual traces from bottom to top). The star on the y-axis represents the threshold stimulus intensity. The different ABR peaks are labeled using roman numerals. (B) ABRs recorded from one CBA/CaJ mouse in response to pure-tone pips of increasing frequency (individual panels from bottom to top). Each panel shows the mean response (in color) averaged over 500 repeats. The black stippled line in each panel shows the mean response (± standard error) averaged over a population of 5 animals. The shaded areas in light green and pink indicate the timing of waves I and V respectively. (C) Amplitude of wave I vs. wave V at each of the frequencies we tested. Open circles represent the data obtained from individual animals. The lines join the mean values across different frequencies.

Mentions: To study the frequency sensitivity of different areas along the ascending auditory pathway, we first recorded auditory brainstem responses to clicks (Fig 1A) and tones of varying frequencies (Fig 1B). ABRs are evoked potentials which typically occur within the first 10 ms after stimulus onset and consist of a series of positive-to-negative waves that reflect the synchronized neural activity in the auditory nerve and subsequent nuclei within the auditory brainstem [19, 29–31]. Fig 1B shows tone-evoked ABRs obtained from a representative mouse at 10 dB above threshold (solid lines) along with the ABRs averaged over all 5 animals in the sample population (black stippled lines). There were clear frequency-dependent differences in the ABR waveforms, to the extent that the early peaks were difficult to discern for high frequencies, and the late peaks were difficult to discern for low frequencies. To quantify the differences in the frequency sensitivity between peripheral and central areas, we measured the amplitude of wave I (green shaded area) and the amplitude of wave V (pink shaded area). We focused on waves I and V because they reflect the first stage of processing in the AN/CN and the final stage of brainstem processing in the IC, which serves as the hub of the central auditory pathway where inputs from all of the other brainstem nuclei are integrated for transmission to the thalamocortical circuit (for definition of waves I and V, see Methods). We found that across the population, increasing the stimulus frequency lead to a decrease in the amplitude of wave I. In contrast, the amplitude of wave V increased as the stimulus frequency was increased (Fig 1C; ANOVA, p < 0.01 for both waveform components). Tone-evoked ABRs can be difficult to interpret as they have not yet been widely studied in mice [18], but the increase in the amplitude of wave V relative to wave I with increasing frequency suggests an increase in IC activity relative to that in the periphery [32, 33]. A study of the likely cellular generators of ABR peaks (in cats) suggests that increasing how many neurons contribute and/or how strongly they synchronize their firing in response to sounds increases the amplitude of the corresponding ABR peak [34]. Thus, we hypothesized that the high ultrasonic frequencies that comprise many mouse vocalizations may be overrepresented in the central auditory system. We investigated this hypothesis in more detail using single- and multi-unit recordings to characterize the responses of neurons at different stages along the auditory pathway with high resolution.


An Overrepresentation of High Frequencies in the Mouse Inferior Colliculus Supports the Processing of Ultrasonic Vocalizations.

Garcia-Lazaro JA, Shepard KN, Miranda JA, Liu RC, Lesica NA - PLoS ONE (2015)

Auditory brainstem responses to click and tone stimuli.(A) ABRs recorded from one CBA/CaJ mouse in response to clicks of increasing intensity (individual traces from bottom to top). The star on the y-axis represents the threshold stimulus intensity. The different ABR peaks are labeled using roman numerals. (B) ABRs recorded from one CBA/CaJ mouse in response to pure-tone pips of increasing frequency (individual panels from bottom to top). Each panel shows the mean response (in color) averaged over 500 repeats. The black stippled line in each panel shows the mean response (± standard error) averaged over a population of 5 animals. The shaded areas in light green and pink indicate the timing of waves I and V respectively. (C) Amplitude of wave I vs. wave V at each of the frequencies we tested. Open circles represent the data obtained from individual animals. The lines join the mean values across different frequencies.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4526676&req=5

pone.0133251.g001: Auditory brainstem responses to click and tone stimuli.(A) ABRs recorded from one CBA/CaJ mouse in response to clicks of increasing intensity (individual traces from bottom to top). The star on the y-axis represents the threshold stimulus intensity. The different ABR peaks are labeled using roman numerals. (B) ABRs recorded from one CBA/CaJ mouse in response to pure-tone pips of increasing frequency (individual panels from bottom to top). Each panel shows the mean response (in color) averaged over 500 repeats. The black stippled line in each panel shows the mean response (± standard error) averaged over a population of 5 animals. The shaded areas in light green and pink indicate the timing of waves I and V respectively. (C) Amplitude of wave I vs. wave V at each of the frequencies we tested. Open circles represent the data obtained from individual animals. The lines join the mean values across different frequencies.
Mentions: To study the frequency sensitivity of different areas along the ascending auditory pathway, we first recorded auditory brainstem responses to clicks (Fig 1A) and tones of varying frequencies (Fig 1B). ABRs are evoked potentials which typically occur within the first 10 ms after stimulus onset and consist of a series of positive-to-negative waves that reflect the synchronized neural activity in the auditory nerve and subsequent nuclei within the auditory brainstem [19, 29–31]. Fig 1B shows tone-evoked ABRs obtained from a representative mouse at 10 dB above threshold (solid lines) along with the ABRs averaged over all 5 animals in the sample population (black stippled lines). There were clear frequency-dependent differences in the ABR waveforms, to the extent that the early peaks were difficult to discern for high frequencies, and the late peaks were difficult to discern for low frequencies. To quantify the differences in the frequency sensitivity between peripheral and central areas, we measured the amplitude of wave I (green shaded area) and the amplitude of wave V (pink shaded area). We focused on waves I and V because they reflect the first stage of processing in the AN/CN and the final stage of brainstem processing in the IC, which serves as the hub of the central auditory pathway where inputs from all of the other brainstem nuclei are integrated for transmission to the thalamocortical circuit (for definition of waves I and V, see Methods). We found that across the population, increasing the stimulus frequency lead to a decrease in the amplitude of wave I. In contrast, the amplitude of wave V increased as the stimulus frequency was increased (Fig 1C; ANOVA, p < 0.01 for both waveform components). Tone-evoked ABRs can be difficult to interpret as they have not yet been widely studied in mice [18], but the increase in the amplitude of wave V relative to wave I with increasing frequency suggests an increase in IC activity relative to that in the periphery [32, 33]. A study of the likely cellular generators of ABR peaks (in cats) suggests that increasing how many neurons contribute and/or how strongly they synchronize their firing in response to sounds increases the amplitude of the corresponding ABR peak [34]. Thus, we hypothesized that the high ultrasonic frequencies that comprise many mouse vocalizations may be overrepresented in the central auditory system. We investigated this hypothesis in more detail using single- and multi-unit recordings to characterize the responses of neurons at different stages along the auditory pathway with high resolution.

Bottom Line: Auditory brainstem response measurements suggested stronger responses in the midbrain relative to the periphery for frequencies higher than 32 kHz.This result was confirmed by single- and multi-unit recordings showing that high ultrasonic frequency tones and vocalizations elicited responses from only a small fraction of cells in the periphery, while a much larger fraction of cells responded in the inferior colliculus.These results suggest that the processing of communication calls in mice is supported by a specialization of the auditory system for high frequencies that emerges at central stations of the auditory pathway.

View Article: PubMed Central - PubMed

Affiliation: Ear Institute, University College London, 332 Grays Inn Road, London, WC1X 8EE, United Kingdom.

ABSTRACT
Mice are of paramount importance in biomedical research and their vocalizations are a subject of interest for researchers across a wide range of health-related disciplines due to their increasingly important value as a phenotyping tool in models of neural, speech and language disorders. However, the mechanisms underlying the auditory processing of vocalizations in mice are not well understood. The mouse audiogram shows a peak in sensitivity at frequencies between 15-25 kHz, but weaker sensitivity for the higher ultrasonic frequencies at which they typically vocalize. To investigate the auditory processing of vocalizations in mice, we measured evoked potential, single-unit, and multi-unit responses to tones and vocalizations at three different stages along the auditory pathway: the auditory nerve and the cochlear nucleus in the periphery, and the inferior colliculus in the midbrain. Auditory brainstem response measurements suggested stronger responses in the midbrain relative to the periphery for frequencies higher than 32 kHz. This result was confirmed by single- and multi-unit recordings showing that high ultrasonic frequency tones and vocalizations elicited responses from only a small fraction of cells in the periphery, while a much larger fraction of cells responded in the inferior colliculus. These results suggest that the processing of communication calls in mice is supported by a specialization of the auditory system for high frequencies that emerges at central stations of the auditory pathway.

No MeSH data available.


Related in: MedlinePlus