Development of single- and two-tone responses of anteroventral cochlear nucleus neurons in gerbil¹

Abstract

Responses of anteroventral cochlear nucleus (AVCN) neurons in developing gerbils were obtained to single-tone stimuli, and two-tone stimuli elicited by best frequency probes presented over a range of intensities. Neurons displayed Type I, Type I/III, and Type III receptive field patterns. Best frequencies ranged from 1.5 to 10.0 kHz. Two-tone suppression (2TS) was first observed in 5 of 16 neurons examined at 14 dab, and in all neurons examined in gerbils aged 15 to 60 dab. Suppression areas grew larger, and discharge rate reductions became greater with age. Features of the two-tone responses that were highly correlated with single-tone responses across age groups include maximum rate reductions and suppression area thresholds. The intensity level of the CF probe-tone also influenced these features of 2TS. Maximum rate reductions to below spontaneous rate levels of activity were common across age groups. Results suggest that the cochlear amplifier is present and fundamentally adult-like by 15 dab for the regions of the cochlea coding the mid frequencies in gerbil. Over the subsequent week, contributions to the developing two-tone responses by the cochlear amplifier increase slightly. Two-tone responses are influenced by central inhibitory mechanisms as early as 14 dab.

Introduction

Two-tone suppression (2TS) can be operationally defined as the decrease in activity evoked by one tone (the probe) that occurs when it is presented together with a second tone (the suppressor). Suppression in mammals depends on the presence and correct functioning of the outer hair cells. It is thought to be generated by the normal operating characteristics of physiologically active cochlear processes (Dallos et al., 1980; Schmiedt et al., 1980; Schmiedt and Zwislocki, 1980; Mills and Schmiedt, 1983; Patuzzi and Robertson, 1988). These processes, collectively termed the cochlear amplifier, are also responsible for the high degree of sensitivity and frequency tuning exhibited by the healthy cochlea.

Cochlear responses to single- and two-tone stimuli are intrinsically linked. The cochlear amplifier boosts vibratory responses, primarily to low level stimuli, near the basilar membrane place which codes the input frequency (e.g. Neely and Kim, 1983, Neely and Kim, 1986; Yates et al., 1992). It is thought that suppression of a given probe-tone's response takes place where the suppressor-tone itself engages and saturates the cochlear amplifier in the probe's characteristic frequency (CF) region, rendering it unavailable to amplify probe induced activity (Geisler et al., 1990). Therefore, it is hypothesized that 2TS can be used to infer the contribution of the cochlear amplifier to probe-driven discharge activity.

Cochlear sensitivity and tuning improve postnatally in altricial mammals (for review, see Rübsamen, 1992; Walsh and Romand, 1992; Rübsamen and Lippe, 1998). In the Mongolian gerbil (Meriones unguiculatus), auditory responses are first able to be observed at 12 days after birth (dab) using cochlear microphonic techniques (Woolf and Ryan, 1984). Adult-like sensitivity and tuning is reached in the majority of auditory nerve fibers and cochlear nucleus neurons by approximately 18 to 21 dab (Woolf and Ryan, 1985; Echteler et al., 1989).

In addition to changes in cochlear function in altricial animals, postnatal alterations in cochlear structures have also been observed in a variety of species (for review see Rubel, 1978; Walsh and Romand, 1992). Certain of these changes could affect cochlear function through alterations of basilar membrane mass and stiffness characteristics. Other changes, including a dramatic increase in the endocochlear potential (cat: Fernandez and Hinojosa, 1974; gerbil: Woolf et al., 1986; McGuirt et al., 1995; rat: Bosher and Warren, 1971), are thought to influence cochlear response properties through changes in the processes underlying the cochlear amplifier.

The development of those cochlear response properties which are likely to be produced primarily by active cochlear processes has been examined extensively using distortion product otoacoustic emissions (DPOAEs) (gerbil: Norton et al., 1991; Mills et al., 1994, Mills and Rubel, 1996; rat: Henley et al., 1989; Lenoir and Puel, 1987), and less often using 2TS (cat: Fitzakerley et al., 1994a, Fitzakerley et al., 1994b). These studies have shown that the cochlear amplifier does, in fact, mature postnatally in altricial animals. However, the relationship between the ontogeny of the cochlear amplifier and the maturation of cochlear sensitivity and tuning has not been fully characterized.

The present study has two parts. The first investigates the development of responses elicited by two-tone stimulation of mid frequency primary-like neurons in the AVCN. Relationships between features of 2TS and neuronal response properties are examined at various developmental time points. Both the rate reduction produced by high level suppressors (2TS magnitude) and the shapes of suppression areas (2TS area thresholds and bandwidths) are examined. Data from the only other investigations of the development of two-tone rate suppression (Fitzakerley et al., 1994a, Fitzakerley et al., 1994b) showed a large amount of variability which obscured any systematic relationship between emerging neuronal tip regions and the ontogeny of 2TS. It was therefore a goal in the present study to ensure that maximum 2TS was obtained by using a broad range of suppressor- and probe-tone combinations.

The second part of this study attempts to relate some of the observed age-related changes in 2TS to changes in the amount of CF amplification supplied to the probe-tone's response, and to provide some insight into possible contributions to the AVCN two-tone response by neural inhibition. Suppression is examined over a range of probe-tone intensity levels. Comparisons are made between effects on 2TS caused by changes in age and in the level of the probe. It was hypothesized that for a given neuron, increasing the level of the probe would cause a systematic reduction in the amplification of the probe's basilar membrane response (e.g. Rhode, 1978, Ruggero and Rich, 1991) and thus reduce cochlear 2TS (Ruggero et al., 1992). On the other hand, we propose that increasing the probe intensity might cause an increase in contributions to the two-tone responses by cochlear nucleus inhibition.