Stimulation of vestibular efferent neurons excites calyx and dimorphic (CD) afferents. This excitation consists of fast and slow components that differ Ͼ100-fold in activation kinetics and response duration. In the turtle, efferent-mediated fast excitation arises in CD afferents when the predominant efferent neurotransmitter acetylcholine (ACh) activates calyceal nicotinic ACh receptors (nAChRs); however, it is unclear whether the accompanying efferent-mediated slow excitation is also attributed to cholinergic mechanisms. To identify synaptic processes underlying efferent-mediated slow excitation, we recorded from CD afferents innervating the turtle posterior crista during electrical stimulation of efferent neurons,incombinationwithpharmacologicalprobesandmechanicalstimulation.Efferent-mediatedslowexcitationwasunaffectedbynAChR compounds that block efferent-mediated fast excitation, but were mimicked by muscarine and antagonized by atropine, indicating that it requires ACh and muscarinic ACh receptor (mAChR) activation. Efferent-mediated slow excitation or muscarine application enhanced the sensitivity of CD afferents to mechanical stimulation, suggesting that mAChR activation increases afferent input impedance by closing calyceal potassium channels. These observations were consistent with suppression of a muscarinic-sensitive K ϩ -current, or M-current. Immunohistochemistry for putative M-current candidates suggested that turtle CD afferents express KCNQ3, KCNQ4, and ERG1-3 potassium channel subunits. KCNQ channels were favored as application of the selective antagonist XE991 mimicked and occluded efferent-mediated slow excitation in CD afferents. These data highlight an efferent-mediated mechanism for enhancing afferent sensitivity. They further suggest that the clinical effectiveness of mAChR antagonists in treating balance disorders may also target synaptic mechanisms in the vestibular periphery, and that KCNQ channel modulators might offer similar therapeutic value.
Perception of complex sounds depends on the encoding of the dynamic and static structures within the ongoing stimulus by the auditory system. Aging has been associated with deficits in both areas, thus, the difficulty that the elderly have in speech comprehension could due to hearing loss, or to a loss of temporal sensitivity, or some combination of both. We investigated the effects of sensorineural hearing loss (SNHL) on neural correlates of temporal resolution by recording the responses of inferior colliculus neurons to a gap detection paradigm. We used C57BL/6 (C57) strain of laboratory mouse, which carries the Ahl deafness gene that initiates a progressive high frequency SNHL beginning at about 2 months of age and rapidly progresses to total deafness by 18 months. We compared gap encoding from inferior collicular neurons from young, normal-hearing C57 mice and middle-aged, hearing-impaired, C57 mice, quantifying minimal gap threshold, and recovery functions. The proportion of unit types, spontaneous rates and degree of monotonicity were comparable between young and middle-aged C57 mice. As expected, single unit thresholds were elevated by 30-40 dB in middleaged C57 mice. However, no significant differences in mean minimal gap thresholds or in the slopes of the gap recovery functions were found between the two age groups. Thus, the results suggest that moderate high frequency SNHL does not affect temporal processing as measured by the gap detection paradigm.
Previous research in auditory sequence recognition based on the order of the components has suggested two conflicting hypotheses. This paper explores possible reasons for the conflict, and proposes a "hybrid" hypothesis consistent with the published data: The discrimination of sequences is better when permuted tones belong to a single perceived group, but the order of tones in different perceived groups is available. In the present study, subjects discriminated sequences forming two perceived groups, only one of which contained an order change, and sequences in three control conditions. Even though the experimental condition included order changes in one perceived group as well as among tones in different perceived groups, discrimination performance was significantly worse than in the control conditions, and fell to chance when all conditions were presented in random order. Performance improved significantly when the experimental condition was presented alone. This result supports the hybrid hypothesis, but several alternative explanations are discussed.The perception of auditory sequences has been studied with increasing intensity over the past 20 years, and some interesting suggestions about how such sequences are processed by the auditory system have been made. Nevertheless, a comprehensive theory has yet to emerge.
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