Salicylate and quinine selectively increase spontaneous firing rates in secondary auditory cortex

doi:10.1016/S0378-5955(98)00008-2

Hearing Research

Volume 117, Issues 1–2, March 1998, Pages 149-160

https://doi.org/10.1016/S0378-5955(98)00008-2 Get rights and content

Abstract

This study presents firing rates for simultaneously recorded spontaneous and stimulus driven multi-unit activity in primary auditory cortex (AI), anterior auditory field (AAF) and secondary auditory cortex (AII) in cats before and after application of salicylate or quinine. From 21 cats, in three cortical areas simultaneously, a total of 1533 multi-unit files were obtained. The data suggest (1) that both salicylate and quinine significantly increase spontaneous firing rates in AII, whereas in AI and AAF both quinine and salicylate reduced the spontaneous rate; (2) the effect of both drugs was to increase spontaneous rates for recording sites with high characteristic frequency (CF) and a tendency to decrease them for low CF sites; (3) the mean stimulus driven firing rates were not affected by either drug except for a decrease produced by quinine in AI; (4) changes in driven firing rate were positively correlated with changes in spontaneous firing rates. This suggests that tinnitus inducing agents selectively increase spontaneous firing rates in the extralemniscal pathway.

Introduction

The effects of sodium salicylate and quinine on spontaneous firing rates (SR) in the auditory system are likely dependent on the dose, the site of recording and the choice of experimental animal. The effective dose may also be species dependent. The first results reported for cats, that were given 400 mg/kg sodium salicylate i.v., showed an increase of 10–20 spikes per second (sp/s) in the spontaneous discharge of medium-spontaneous rate (20–59 sp/s) auditory nerve fibers (Evans et al., 1981; Evans and Borerwe, 1982). A later study in cats using a lower dose (200 mg/kg) of salicylate did not find a significant increase in the mean spontaneous rates in either of two subpopulations of nerve fibers following drug administration (Stypulkowski, 1990). For high SR fibers in that study the mean decreased non-significantly from 53 sp/s to 52 sp/s. Similarly, the means for the low-medium SR cells were nearly identical (about 6.2 sp/s) for pre-application and post-application conditions. In some individual cells, however, significant increases in firing rate were seen. Salicylate applied into scala media (or scala tympani) of the pigeon (Shehata-Dieler et al., 1994) led either to a slightly increased or to an unchanged spontaneous firing rate in the majority of auditory fibers. The rate changes were more pronounced in the mid- to high-frequency range. A change in distribution of spontaneous firing rate in guinea pig auditory nerve fibers was reported after quinine application (Mulheran, 1990). The percentage of fibers with a low spontaneous firing rate was found to be about 26% in the control group whereas it changed to 47% after quinine application.

Administration of 450 mg/kg of sodium salicylate to guinea pigs caused an increase in the mean population firing rate in inferior colliculus (IC) neurons and produced activity with a much higher regularity of discharges than before. The mode of the interval histogram decreased significantly (Jastreboff and Sasaki, 1986). Also in the IC of guinea pigs, i.v. infusion of 200 mg/kg sodium salicylate increased spontaneous firing rate from about 5 sp/s to about 19 sp/s at 100 min after application and then declined to baseline after 10 h (Manabe et al., 1997). Spontaneous activity of 471 units from the external nucleus of the IC (ICX) in the rat revealed that salicylate (233 mg/kg) increased spontaneous activity from about 6 sp/s to about 9 sp/s. The effect was dominant for units with CFs in the 10–16 kHz range (Chen and Jastreboff, 1995).

In primary auditory cortex (AI) of cats, Ochi and Eggermont (1996Ochi and Eggermont, 1997) investigated the effect of salicylate (200 mg/kg) and quinine (100 or 200 mg/kg) on single-unit firing activity. Recordings from the same units were made prior to application and continuously up to on average 6 h after administration. For both salicylate and quinine, significant changes were found in spontaneous firing rates for two groups of units separately. Low-spontaneous rate units (initial firing rate <1 sp/s) showed an increase in spontaneous rate and high-spontaneous rate units (initial firing rate >1 sp/s) showed a decrease in spontaneous firing rate. No significant change in spontaneous firing rate was found when data were pooled across all units.

These findings suggest three possibilities: (1) either the IC is special for demonstrating effects of salicylate and quinine on spontaneous firing rates, (2) the effects for the same dose are more pronounced in guinea pigs and rats than in cats, or (3) the effects may be more pronounced in the extralemniscal pathway (Møller et al., 1992) of which the ICX is a part. In the latter case one would expect the secondary auditory cortex (AII), which receives a major input from the extralemniscal pathway, to show enhanced spontaneous firing rates after drug application.

The present study presents pre- and post-application firing rates for simultaneously recorded multi-unit activity in three auditory cortical fields in cat: two primary ones AI and AAF (Rouiller et al., 1991) and secondary auditory cortex. We found significant increases in multi-unit firing rate in AII, whereas drug dependent decreases in firing rates in anterior auditory field (AAF) and AI were noted.

Section snippets

Animal preparation

All cats were premedicated with 0.25 ml/kg body weight of a mixture of 0.1 ml acepromazine (0.25 mg/ml) and 0.9 ml of atropine methyl nitrate (0.5 mg/ml) subcutaneously. After about 30 min they received an intramuscular injection of 30 mg/kg of ketamine hydrochloride (100 mg/ml) and an intraperitoneal injection of 20 mg/kg of sodium pentobarbital (65 mg/ml). The head was shaved, an incision was made in the skin overlying the skull, Duracaine^® (a mixture of lidocaine hydrochloride and

Results

Recordings were made in 21 healthy cats (five cats for salicylate application, seven cats for quinine application, and nine control cats). The cats were from 60 days to 150 days old (mean=85 days), for salicylate they were from 77 days to 92 days (mean=85 days), for quinine from 62 days to 150 days (mean=89 days), and for the control cats from 60 to 100 days (mean=81 days). From three cortical areas simultaneously, 108 multi-unit recordings were obtained for 15 min of silence each, 102

Discussion

Our data suggest (1) that both salicylate and quinine significantly increase spontaneous firing rates in AII. In AI and AAF, both quinine and salicylate reduced the spontaneous rate; (2) the effect of both drugs was to increase spontaneous rates for high CF sites and a tendency to decrease them for low CF sites; (3) the mean driven firing rates were not affected by either drug except for a decrease produced by quinine in AI; (4) changes in driven firing rate were positively correlated with

Acknowledgements

This investigation was supported by grants from the Alberta Heritage Foundation for Medical Research, the Natural Sciences and Engineering Research Council of Canada, and the American Tinnitus Association.

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View full text

Salicylate and quinine selectively increase spontaneous firing rates in secondary auditory cortex

Abstract

Introduction

Section snippets

Animal preparation

Results

Discussion

Acknowledgements

Salicylate-induced abnormal activity in the inferior colliculus of rats

Hear. Res.

Neural interaction in cat primary auditory cortex. Dependence on recording depth, electrode separation and age

J. Neurophysiol.

Differential maturation rates for response parameters in cat primary auditory cortex

Audit. Neurosci.

Firing rate and firing synchrony distinguish dynamic from steady state sound

NeuroReport

Ototoxic effects of salicylates on the responses of single cochlear nerve fibres and on cochlear potentials

Br. J. Audiol.

Salicylate-induced changes in spontaneous activity of single units in the inferior colliculus of the guinea pig

J. Acoust. Soc. Am.

Increases in spontaneous activity in the dorsal cochlear nucleus following exposure to high intensity sound: a possible neural correlate of tinnitus

Audit. Neurosci.

Salicylate and quinine affect the central nervous system

Hear. Res.

Spontaneous spike discharges from single units in the cochlear nucleus after destruction of the cochlea

Exp. Neurol.

Auditory-nerve responses from cats raised in a low-noise chamber

J. Acoust. Soc. Am.

Acoustic Trauma in cats. Cochlear pathology and auditory-nerve activity

Acta Otolaryngol.