A novel cholinergic "slow effect" of efferent stimulation on cochlear potentials in the guinea pig

Abstract

This report documents slow changes in cochlear responses produced by electrical stimulation of the olivocochlear bundle (OCB), which provides efferent innervation to the hair cells of the cochlea. These slow changes have time constants of 25–50 sec, three orders of magnitude slower than those reported previously. Such “slow effects” are similar to classically described “fast effects” in that (1) they comprise a suppression of the compound action potential (CAP) of the auditory nerve mirrored by an enhancement of the cochlear microphonic potential (CM) generated largely by the outer hair cells; (2) the magnitude of suppression decreases as the intensity of the acoustic stimulus increases; (3) they share the same dependence on OCB stimulation rate; (4) both are extinguished upon cutting the OCB; and (5) both are blocked with similar concentrations of a variety of cholinergic antagonists as well as with strychnine and bicuculline. These observations suggest that both fast and slow effects are mediated by the same receptor and are produced by conductance changes in outer hair cells. Slow effects differ from fast effects in that (1) fast effects are greatest for acoustic stimulus frequencies between 6 and 10 kHz, whereas slow effects peak for frequencies from 12 to 16 kHz, and (2) fast effects persist over long periods of OCB stimulation, whereas slow effects diminish after 60 sec of stimulation. The time course of the slow effects can be described mathematically by assuming that each shock-burst produces, in addition to a fast effect, a small decrease in CAP amplitude that decays exponentially with a time constant that is long relative to the intershock interval. The long time constant of the slow effect compared to the fast effect suggests that it may arise from a distinct intracellular mechanism, possibly mediated by second- messenger systems.

Effects of Electrical Stimulation of Olivocochlear Fibers in Cochlear Potentials in the Chinchilla

“…These negative slopes of the efferent-induced CAP reductions would indicate the presence of slow MOC effects for highfrequency stimuli. A similar dependence of fast and slow effects on stimulus frequency has been observed in guinea pig (Sridhar et al 1995), in which the fast effect had a larger peak around 8-10 kHz, while the slow effect had a smaller peak for higher frequencies (around 14 kHz). As mentioned above, we found the greatest CAP decrease around 2 kHz, and a secondary peak of CAP reduction near 8 kHz that could reflect both, fast and slow effects in the chinchilla.…”

“…reported for the cat (Galambos 1956;Fex 1959;Desmedt 1962;Sohmer 1965;Wiederhold and Peake 1966;Gifford and Guinan 1987) and the guinea pig (Sridhar et al 1995;Murugasu and Russell 1996), although in most cases they were of smaller magnitudes. In our measurements, we found efferent-produced CAP reductions of up to a maximum of 11 dB, compared with reductions near or over 20 dB observed in cats (Desmedt and Monaco 1961;Wiederhold 1970;Gifford and Guinan 1987).…”

“…Two types of MOC efferent effects have been described; fast effects that take place with time constants in the order of tens of milliseconds, and slow effects that occur with time constants three orders of magnitude larger (Sridhar et al 1995;Cooper and Guinan 2003). Our experimental paradigm was best suited to measure fast MOC effects by evaluating the change in amplitude of cochlear potentials recorded at the onset of the efferent stimulation series (30 ms after delivery of electric pulses at the floor of the fourth ventricle).…”

Inner ear drug delivery via a reciprocating perfusion system in the guinea pig

“…The practice of placing drugs of interest within cochlear perilymphatic spaces via a perfusion technique is a method with a long history of successful application (e.g., [32][33][34][35][36][37][38][39][40][41][42]). When carefully administered, the technique itself has been shown to have little effect on a variety of gross cochlear and neural potentials as recorded from sites within and near the cochlea (e.g., [43]).…”

Efferent Actions in the Chinchilla Vestibular Labyrinth

“…Because of the slow kinetics involved, it is natural to suspect metabotropic receptors. At the same time, it should be noted that fast and slow efferent effects in the mammalian cochlea may involve the same nicotinic receptor (Sridhar et al 1995(Sridhar et al , 1997. Efferent neurons contain CGRP (Tanaka et al 1988(Tanaka et al , 1989Wackym et al 1991;Ishiyama et al 1994) and possibly other neuroactive peptides (for review, see Goldberg et al 1999).…”