Primary vestibular afferents transmit information from hair cells about head position and movement to the CNS, which is critical for maintaining balance, gaze stability and spatial navigation. The CNS, in turn, modulates hair cells and afferents via the efferent vestibular system (EVS) and its activation of several cholinergic signaling mechanisms. Electrical stimulation of EVS neurons gives rise to three kinetically- and mechanistically-distinct afferent responses including a slow excitation, a fast excitation, and a fast inhibition.
View Article and Find Full Text PDFThe peripheral vestibular system detects head position and movement through activation of vestibular hair cells (HCs) in vestibular end organs. HCs transmit this information to the CNS by way of primary vestibular afferent neurons. The CNS, in turn, modulates HCs and afferents via the efferent vestibular system (EVS) through activation of cholinergic signaling mechanisms.
View Article and Find Full Text PDFStimulation of cholinergic efferent neurons innervating the inner ear has profound, well-characterized effects on vestibular and auditory physiology, after activating distinct ACh receptors (AChRs) on afferents and hair cells in peripheral endorgans. Efferent-mediated fast and slow excitation of vestibular afferents are mediated by α4β2*-containing nicotinic AChRs (nAChRs) and muscarinic AChRs (mAChRs), respectively. On the auditory side, efferent-mediated suppression of distortion product otoacoustic emissions (DPOAEs) is mediated by α9α10nAChRs.
View Article and Find Full Text PDFElectrical stimulation of the mammalian efferent vestibular system (EVS) predominantly excites primary vestibular afferents along two distinct time scales. Although roles for acetylcholine (ACh) have been demonstrated in other vertebrates, synaptic mechanisms underlying mammalian EVS actions are not well-characterized. To determine if activation of ACh receptors account for efferent-mediated afferent excitation in mammals, we recorded afferent activity from the superior vestibular nerve of anesthetized C57BL/6 mice while stimulating EVS neurons in the brainstem, before and after administration of cholinergic antagonists.
View Article and Find Full Text PDFMuscarinic receptor antagonists act as potent inducers of oligodendrocyte differentiation and accelerate remyelination. However, the use of muscarinic antagonists in the clinic is limited by poor understanding of the operant receptor subtype, and questions regarding possible species differences between rodents and humans. Based on high selective expression in human oligodendrocyte progenitor cells (OPCs), we hypothesized that MR is the functionally relevant receptor.
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