Classification of unit types in the anteroventral cochlear nucleus of laboratory mice

Abstract

This report introduces a system for the objective physiological classification of single-unit activity in the anteroventral cochlear nucleus (AVCN) of anesthetized CBA/129 and CBA/CaJ mice. As in previous studies, the decision criteria are based on the temporal properties of responses to short tone bursts that are visualized in the form of peri-stimulus time histograms (PSTHs). Individual unit types are defined by the statistical distribution of quantifiable metrics that relate to the onset latency, regularity, and adaptation of sound-driven discharge rates. Variations of these properties reflect the unique synaptic organizations and intrinsic membrane properties that dictate the selective tuning of sound coding in the AVCN. When these metrics are applied to the mouse AVCN, responses to best frequency (BF) tones reproduce the major PSTH patterns that have been previously demonstrated in other mammalian species. The consistency of response types in two genetically diverse strains of laboratory mice suggests that the present classification system is appropriate for additional strains with normal peripheral function. The general agreement of present findings to established classifications validates laboratory mice as an adequate model for general principles of mammalian sound coding. Nevertheless, important differences are noted for the reliability of specialized endbulb transmission within the AVCN, suggesting less secure temporal coding in this high-frequency species.

Fig. 1

Exemplars displaying the definitive response patterns of four major AVCN response types: (A) Pri, (B) Pri-N, (C) Ch-S, and (D) Ch-T. Left: Dot rasters showing spike times relative to stimulus onset for 270 repetitions of a 50-ms BF tone. Right: PSTHs summarizing the temporal distributions of the dot rasters.

Fig. 2

Decision tree for unit classification. Major branch points are defined by the regularity of onset discharge rates (Criterion 1), the separability of 1^st and 2^nd spike latencies (Criterion 2), and transient versus slow rates of adaptation (Criteria 3 and 4).

Fig. 3

Criterion 1 of the decision tree. Units were assigned to generic primarylike (Pri) or chopper (Ch) categories based on an analysis of regularity. A and B: The CV scores of the four exemplars in Fig. 1 illustrate differences in the regularity of primarylike and chopper units. Classification was based on CV-E scores at stimulus onset (left inset). The gray-filled area delineates the ambiguous zone between the two response types. C: Histograms comparing the distribution of CV-E scores for Pri and Ch exemplars. Remaining units were categorized as generic chopper or primarylike responses if their CV-E scores coincided with either exemplar distribution. Units with ambiguous scores were not further categorized (NFC). Numerical labels show the location of the four exemplars in A and B.

Fig. 4

Criterion 2 of the decision tree. Pri-N subtypes were separated from Pri units by the precision of FSLs. A: Temporally expanded dot rasters showing only the first and second spike latencies of the Pri and Pri-N exemplars in Fig. 1. B: Histograms of the first and second spike latencies. C: The mean and standard deviation of first (filled) and second spike latencies (unfilled) for 9 Pri and 5 Pri-N exemplars. The units have been rank ordered by their JSD scores. D: Two-dimensional scatter plot of FSL_SD and JSD. Generic Pri units were objectively categorized if their scores fell within regions defined by Pri and Pri-N exemplars. Units with ambiguous scores were not further categorized (Pri-NFC).

Fig. 5

Criterion 3 of the decision tree. Ch-T were distinguished from generic Ch-S units by non-linear adaptation effects. A: Mean ISI functions for the Ch-S and Ch-T exemplars in Fig. 1. The Ch-T unit exhibited rapid adaptation near the beginning of the stimulus. This sharp increase in ISI was quantified by ISI_AR and ISI_MS statistics. Shaded regions indicate time intervals that were used in the calculation of ISI_AR. Line segment marks ISI_MS. B: Two-dimensional scatter plot showing the mutual separation of ISI_AR and ISI_MS among Ch-S and Ch-T exemplars. Additional generic chopper units were classified as Ch-S or Ch-T if their scores were associated with exemplars. One generic Ch unit resided in an ambiguous region and was not further categorized (Ch-NFC)

Fig. 6

Criterion 4 of the decision tree. Slowly adapting Ch-SA units were isolated from generic Ch-S units by linear adaptation effects that persisted throughout the stimulus presentation. A: Mean ISI functions for the Ch-S exemplar in Fig. 1 and a typical Ch-SA unit. B: CV functions for the same units. Shaded regions indicate the time intervals that were used to compute ISI_AS and CV-L scores. C: Two-dimensional scatter plot of ISI_AS and CV-L scores for Ch-S exemplars and units that were originally assigned to the Ch-S category because they did not show transient adaptation. Units that were aligned beyond the range of Ch-S exemplars were assigned to the Ch-SA category. Outliers were not further classified (Ch-NFC).

Fig. 7

Objectively categorized units displaying the same response patterns as the Pri, Pri-N, Ch-S, and Ch-T exemplars in Fig. 1. Plotting conventions are described in that figure.

Fig. 8

Spike waveforms of AVCN units in domestic cats (A) and laboratory mice (B). Individual waveforms of PP1 units show large prepotentials (arrows). PP2 units display a small prepotential that is made visible by the averaging of multiple waveforms. The waveforms of PP3 units do not display a prepotential. PP1 and PP2 responses typically precede monophasic action potentials that were not observed in mice. Waveforms of cats are adapted from Bourk 1976; waveforms of mice show the averages of multiple units with the same PSTH classification. Amplitude scale refers to individual traces from the two units in the leftmost panels of A. Time scale refers to all traces.

Fig. 9

Basic response properties of physiologically classified AVCN units. A: BF thresholds. B: Q₁₀ values. C: Spontaneous rates. D: First spike latencies. Symbols indicate the physiological classification of individual units. Numerical labels identify the four exemplars in Fig. 1. Dashed lines describe the best thresholds and average Q₁₀ values of auditory nerve fibers (ANF) using data from Taberner and Liberman, 2005.