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bioRxiv · 10.1101/2020.04.15.041491

Cholinergic modulation of membrane properties of calyx terminals in the vestibular periphery

Ramakrishna, Y.·Manca, M.·Sadeghi, S. G.
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Abstract

Vestibular nerve afferents are divided into regular and irregular groups based on the variability of interspike intervals in their resting discharge. Most afferents receive inputs from bouton terminals that contact type II hair cells as well as from calyx terminals that cover the basolateral walls of type I hair cells. Calyces have an abundance of different subtypes of KCNQ (Kv7) potassium channels and muscarinic acetylcholine receptors (mAChRs) and receive cholinergic efferent inputs from neurons in the brainstem. We investigated whether mAChRs affected membrane properties and firing patterns of calyx terminals through modulation of KCNQ channel activity. Patch clamp recordings were performed from calyx terminals in central regions of the cristae of the horizontal and anterior canals in 13 - 18 day old Sprague-Dawley rats. KCNQ mediated currents were observed as voltage sensitive currents with slow kinetics (activation and deactivation), resulting in spike frequency adaptation so that calyces at best fired a single action potential at the beginning of a depolarizing step. Activation of mAChRs by application of oxotremorine methiodide or inhibition of KCNQ channels by linopirdine dihydrochloride decreased voltage activated currents by [~]30%, decreased first spike latencies by [~]40%, decreased spike thresholds by [~]50%, and resulted in continuous firing during depolarizing steps. Interestingly, some of the calyces showed spontaneous discharge in the presence of these drugs. Together, these findings suggest that cholinergic efferents can modulate the response properties and encoding of head movements by afferents.

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Ramakrishna, Y., Manca, M., Sadeghi, S. G.. 2020-04-17. Cholinergic modulation of membrane properties of calyx terminals in the vestibular periphery. https://doi.org/10.1101/2020.04.15.041491

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