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bioRxiv · 10.1101/2025.02.12.637882

Neuromodulation of the endbulb of Held synapse in the cochlear nucleus

Groshkova, M. B.·Alvanos, T.·Qi, Y.·Wang, F.·Wichmann, C.·Hua, Y.·Moser, T.
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Abstract

Synapses vary greatly in synaptic strength and plasticity, even within the same circuitry or set of pre- and postsynaptic neurons. Neuromodulation is a candidate mechanism to explain some of this variability. Neuromodulators such as monoamines can differentially regulate presynaptic function as well as neuronal excitability. Variability is found also for the large calyceal synapses of the auditory pathway that are endowed with high synaptic vesicle (SV) release probability (Pvr) and large postsynaptic currents enabling reliable and temporally precise transmission of auditory information. Here we investigated whether the calyceal endbulb of Held synapse formed by auditory nerve fibers onto bushy cells (BCs) in the anteroventral cochlear nucleus (AVCN) is modulated by norepinephrine (NE) and serotonin (5-HT). Using electron microscopy (EM) of the cochlear nucleus we found evidence for putative monoaminergic varicosities in both ventral and dorsal divisions. Immunostaining for vesicular 5-HT and NE transporters revealed NE-containing and 5-HT-containing varicosities in the AVCN, juxtaposed to both endbulbs and BCs. Furthermore, we detected immunofluorescence for 5-HT1B, 5-HT4, 5-H7 receptors (R) and 2C-adrenergic receptors (AR) in BCs. We used voltage-clamp recordings from mouse BCs in order to uncover potential presynaptic effects of neuromodulation, which revealed an increase in frequency of miniature excitatory postsynaptic currents (mEPSCs) upon application of NE but not 5-HT. Evoked synaptic transmission was unaffected by the application of either NE or 5-HT. Likewise, while studying the biophysical properties of the BCs, we did not observe effects of NE or 5-HT on low-voltage-activated K+ (K+LVA) and hyperpolarization-activated mixed cation (HCN) channels during application. In summary, we report evidence for the presence of monoaminergic innervation in the cochlear nucleus and for subtle functional NE-neuromodulation at the endbulb of Held synapse.

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Groshkova, M. B., Alvanos, T., Qi, Y., Wang, F., Wichmann, C., Hua, Y., Moser, T.. 2025-02-13. Neuromodulation of the endbulb of Held synapse in the cochlear nucleus. https://doi.org/10.1101/2025.02.12.637882

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