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  • Title: Activity-Dependent Calcium Signaling in Neurons of the Medial Superior Olive during Late Postnatal Development.
    Author: Franzen DL, Gleiss SA, Kellner CJ, Kladisios N, Felmy F.
    Journal: J Neurosci; 2020 Feb 19; 40(8):1689-1700. PubMed ID: 31949105.
    Abstract:
    The development of sensory circuits is partially guided by sensory experience. In the medial superior olive (MSO), these refinements generate precise coincidence detection to localize sounds in the azimuthal plane. Glycinergic inhibitory inputs to the MSO, which tune the sensitivity to interaural time differences, undergo substantial structural and functional refinements after hearing onset. Whether excitation and calcium signaling in the MSO are similarly affected by the onset of acoustic experience is unresolved. To assess the time window and mechanism of excitatory and calcium-dependent refinements during late postnatal development, we quantified EPSCs and calcium entry in MSO neurons of Mongolian gerbils of either sex raised in a normal and in an activity altered, omnidirectional white noise environment. Global dendritic calcium transients elicited by action potentials disappeared rapidly after hearing onset. Local synaptic calcium transients decreased, leaving a GluR2 lacking AMPAR-mediated influx as the only activity-dependent source in adulthood. Exposure to omnidirectional white noise accelerated the decrease in calcium entry, leaving membrane properties unaffected. Thus, sound-driven activity accelerates the excitatory refinement and shortens the period of activity-dependent calcium signaling around hearing onset. Together with earlier reports, our findings highlight that excitation, inhibition, and biophysical properties are differentially sensitive to distinct features of sensory experience.SIGNIFICANCE STATEMENT Neurons in the medial superior olive, an ultra-fast coincidence detector for sound source localization, acquire their specialized function through refinements during late postnatal development. The refinement of inhibitory inputs that convey sensitivity to relevant interaural time differences is instructed by the experience of sound localization cues. Which cues instruct the refinement of excitatory inputs, calcium signaling, and biophysical properties is unknown. Here we demonstrate a time window for activity- and calcium-dependent refinements limited to shortly after hearing onset. Exposure to omnidirectional white noise, which suppresses sound localization cues but increases overall activity, accelerates the refinement of calcium signaling and excitatory inputs without affecting biophysical membrane properties. Thus, the refinement of excitation, inhibition, and intrinsic properties is instructed by distinct cues.
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