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bioRxiv · 10.1101/2022.01.05.475100

Synaptic plasticity of inhibitory synapses onto medial olivocochlear efferent neurons

Cadenas, L. T.·Cheng, H.·Weisz, C. J. C.
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Abstract

The descending auditory system modulates the ascending system at every level. The final descending, or efferent stage, is comprised of lateral olivocochlear (LOC) and medial olivocochlear (MOC) neurons. MOC somata in the ventral brainstem project axons to the cochlea to synapse onto outer hair cells (OHC), inhibiting OHC-mediated cochlear amplification. MOC suppression of OHC function is implicated in cochlear gain control with changing sound intensity, detection of salient stimuli, attention, and protection against acoustic trauma. Thus, sound excites MOC neurons to provide negative feedback of the cochlea. Sound also inhibits MOC neurons via medial nucleus of the trapezoid body (MNTB) neurons. However, MNTB-MOC synapses exhibit short-term depression, suggesting reduced MNTB-MOC inhibition during sustained stimuli. Further, due to high rates of both baseline and sound-evoked activity in MNTB neurons in vivo, MNTB-MOC synapses may be tonically depressed. To probe this, we characterized short-term plasticity of MNTB-MOC synapses in mouse brain slices. We mimicked in vivo-like temperature and extracellular calcium conditions, and in vivo-like activity patterns of fast synaptic activation rates, sustained activation, and prior tonic activity. Synaptic depression was sensitive to extracellular calcium concentration and temperature. During rapid MNTB axon stimulation, post-synaptic currents (PSCs) in MOC neurons summated but with concurrent depression, resulting in smaller, sustained currents, suggesting tonic inhibition of MOC neurons during rapid circuit activity. Low levels of baseline MNTB activity did not significantly reduce responses to subsequent rapid activity that mimics sound stimulation, indicating that, in vivo, MNTB inhibition of MOC neurons persists despite tonic synaptic depression. Key points summaryO_LIInhibitory synapses from MNTB onto MOC neurons exhibit short-term plasticity that is sensitive to calcium and temperature, with enhanced synaptic depression occurring at higher calcium concentrations and at room temperature C_LIO_LIHigh rates of background synaptic activity that mimic the upper limits of spontaneous MNTB activity cause tonic synaptic depression of MNTB-MOC synapses that limits further synaptic inhibition C_LIO_LIHigh rates of activity at MNTB-MOC synapses cause synaptic summation concurrent depression to yield a response with an initial large amplitude that decays to a tonic inhibition C_LI

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Cadenas, L. T., Cheng, H., Weisz, C. J. C.. 2022-01-06. Synaptic plasticity of inhibitory synapses onto medial olivocochlear efferent neurons. https://doi.org/10.1101/2022.01.05.475100

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