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bioRxiv · 10.1101/2022.06.27.497817

Electrical Signaling in Cochlear Efferents is Driven by an Intrinsic Neuronal Oscillator

Hong, H.·Trussell, L. O.
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Abstract

Efferent neurons are believed to play essential roles in maintaining auditory function. The lateral olivocochlear (LOC) neurons, which project from the brainstem to the inner ear where they release multiple transmitters including peptides, catecholamines and acetylcholine, are the most numerous yet least understood elements of efferent control of the cochlea. Using in vitro calcium imaging and patch-clamp recordings, we found that LOC neurons in juvenile and young adult mice exhibited extremely slow waves of activity (~0.1 Hz). These seconds-long bursts of Na+ spikes were driven by an intrinsic oscillator dependent on L-type Ca2+ channels, and were not observed in prehearing mice, suggesting an age-dependent mechanism underlying the intrinsic oscillator. Using optogenetic approaches, we identified both ascending (cochlear nucleus) and descending (auditory cortex) sources of synaptic excitation, as well as the synaptic receptors used for such excitation. Additionally, we identified potent inhibition originating in the glycinergic medial nucleus of trapezoid body (MNTB). Conductance-clamp experiments revealed an unusual mechanism of electrical signaling in LOC neurons, in which synaptic excitation and inhibition served to switch on and off the intrinsically generated spike burst mechanism, allowing for prolonged periods of activity or silence controlled by brief synaptic events. Protracted bursts of action potentials may be essential for effective exocytosis of the diverse transmitters released by LOC fibers in the cochlea. Significance StatementThe lateral olivocochlear (LOC) neurons, being the most abundant auditory efferent control of the ear, remained largely unexplored. Here we reported that LOC neurons displayed patterned electrical activity at an unusually slow pace (~0.1 Hz), mediated by a calcium-dependent intrinsic oscillator. This is surprising given the speed and precision were believed to be the currency of signaling in the lower auditory system. Optogenetic experiments determined the glutamatergic and glycinergic sources of synaptic inputs to these neurons, while conductance-clamp experiments revealed that synaptic activity acts like switches for turning on or off prolonged spike activity driven by the intrinsic oscillator. This extended spike activity may be essential for effective exocytosis of the diverse transmitters released by LOC fibers in the cochlea.

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Hong, H., Trussell, L. O.. 2022-06-30. Electrical Signaling in Cochlear Efferents is Driven by an Intrinsic Neuronal Oscillator. https://doi.org/10.1101/2022.06.27.497817

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