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bioRxiv · 10.1101/2023.07.27.550887

Calcium-sensitive subthreshold oscillations and electrical coupling in principal cells of mouse dorsal cochlear nucleus

Hong, H.·Moore, L. A.·Apostolides, P. F.·Trussell, L. O.
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Abstract

In higher sensory brain regions, slow oscillations (0.5-5 Hz) associated with quiet wakefulness and attention modulate multisensory integration, predictive coding, and perception. Although often assumed to originate via thalamocortical mechanisms, the extent to which sub-cortical sensory pathways are independently capable of slow oscillatory activity is unclear. We find that in the first station for auditory processing, the cochlear nucleus, fusiform cells from juvenile mice (of either sex) generate robust 1-2 Hz oscillations in membrane potential and exhibit electrical resonance. Such oscillations were absent prior to the onset of hearing, intrinsically generated by hyperpolarization-activated cyclic nucleotide-gated (HCN) and persistent Na+ conductances (NaP) interacting with passive membrane properties, and reflected the intrinsic resonance properties of fusiform cells. Cx36-containing gap junctions facilitated oscillation strength and promoted pairwise synchrony of oscillations between neighboring neurons. The strength of oscillations were strikingly sensitive to external Ca2+, disappearing at concentrations > 1.7 mM, due in part to the shunting effect of small-conductance calcium-activated potassium (SK) channels. This effect explains their apparent absence in previous in vitro studies of cochlear nucleus which routinely employed high-Ca2+ extracellular solution. In contrast, oscillations were amplified in reduced Ca2+ solutions, due to relief of suppression by Ca2+ of Na+ channel gating. Our results thus reveal mechanisms for synchronous oscillatory activity in auditory brainstem, suggesting that slow oscillations, and by extension their perceptual effects, may originate at the earliest stages of sensory processing. SIGNIFICANCE STATEMENT (120 words max.)Many studies show that electrical activity in higher brain regions is regulated by brain oscillations. Here we show that such oscillatory activity can arise even in the first levels of auditory processing in the cochlear nucleus of the brainstem (fusiform cells), and is generated not by neural networks but by the biophysical properties of individual neurons. Oscillations are highly sensitive to external Ca2+ due to interplay of multiple ionic conductances. Gap junctions between cells allows for amplification and synchrony of such activity. Oscillations are absent in pre-hearing neurons, suggesting that sound activity might be important for their emergence. We propose that such early-level oscillations may serve to enhance signaling associated with particular environmental stimuli.

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Hong, H., Moore, L. A., Apostolides, P. F., Trussell, L. O.. 2023-07-28. Calcium-sensitive subthreshold oscillations and electrical coupling in principal cells of mouse dorsal cochlear nucleus. https://doi.org/10.1101/2023.07.27.550887

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