Abstract
Descending cholinergic fibers innervate the cochlear nucleus. Spherical bushy cells, principal neurons of the anterior part of the ventral cochlear nucleus, are depolarized by cholinergic agonists on two different time scales. A fast and transient response is mediated by alpha-7 homomeric nicotinic receptors while a slow and long-lasting response is mediated by muscarinic receptors. Spherical bushy cells were shown to express M3 receptors, but the receptor subtypes involved in the slow muscarinic response were not physiologically identified yet. Whole-cell patch clamp recordings combined with pharmacology and immunohistochemistry were performed to identify the muscarinic receptor subtypes and the effector currents involved. Spherical bushy cells also expressed both M1 and M2 receptors. The M1 signal was stronger and mainly somatic while the M2 signal was localized in the neuropil and on the soma of bushy cells. Physiologically, the M-current was observed for the gerbil spherical bushy cells and was inhibited by oxotremorine-M application. Surprisingly, long application of carbachol showed only a transient depolarization. Even though no muscarinic depolarization could be detected, the input resistance increased suggesting a decrease in the cell conductance that matched with the closure of M-channels. The hyperpolarization-activated currents were also affected by muscarinic activation and counteracted the effect of the inactivation of M-current on the membrane potential. We hypothesize that this double muscarinic action might allow adaptation of effects during long durations of cholinergic activation.
Highlights
Cholinergic top-down connections exist at all levels of the auditory pathway to modulate sound information processing [1]
The voltage was first clamped to -20 mV, which activated a substantial amount of Mchannels and keep a constant outward IM (Fig 1B)
Since immunohistochemical results from our previous work pointed out evidence of presynaptic nicotinic receptors [5,10] and we showed the expression of M2 in AVCN, the effect of a cholinergic agonist on the synaptic transmission between auditory nerve and spherical bushy cells (SBC) was evaluated
Summary
Cholinergic top-down connections exist at all levels of the auditory pathway to modulate sound information processing [1]. A well-documented descending system is the olivo-cochlear projection to the inner ear. Cholinergic activation reduces the excitability of the inner ear and facilitates unmasking of sounds in a noisy background by inhibiting the constant response to the noise and reducing wide-spread adaptation [2]. The olivo-cochlear bundle sends collaterals into the cochlear nucleus [2,3,4,5,6,7,8]. About one quarter of cholinergic connections to the ventral cochlear nucleus comes from the pontomesencephalic.
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