Activity-Dependent Calcium Signaling in Neurons of the Medial Superior Olive during Late Postnatal Development

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.

Minimal Number of Required Inputs for Temporally Precise Action Potential Generation in Auditory Brainstem Nuclei

“…We report a significant reduction of the RI in all mature neurons except the MNTB (VNLL: p = 0.029; MNTB: p = 0.95; MSO: p = 0.000053; DNLL: p = 0.000011, Mann-Whitney U). These data corroborated recent reports that MSO neurons undergo loss of GluR2 subunits during late postnatal development (Franzen et al, 2020). Moreover, a developmental change in AMPAR subunit composition can also be expected in the VNLL and DNLL.…”

“…Towards this aim, we first recorded pharmacologically isolated EPSCs evoked by minimal fiber stimulation for each nucleus and age group at a holding potential of −93 mV ( Figure 4A). Corroborating earlier reports, the EPSC amplitude showed a developmental difference in the VNLL [P9/10: 2.5 nA; P23: 7.73 nA, p = 0.00031, Mann-Whitney U (Baumann and Koch, 2017)] and the MSO [P9/10: 0.7 nA; P73: 1.88 nA, p = 0.00079, Mann-Whitney U; Figure 4B (Franzen et al, 2020)]. In the MNTB and DNLL the EPSC size increased slightly, but not significantly (MNTB: P9/10: 9.55 nA; P62: 11.68 nA, p = 0.18, DNLL: P9/10: 0.36 nA; P53: 0.55 nA, p = 0.063, Mann-Whitney U).…”

“…Overall, we describe differential developmental regulations in distinct auditory brainstem nuclei. We suggest furthermore, that these differential regulations arise from different regulatory cues driving development, such as genetic programs, activity (Clause et al, 2014;Franzen et al, 2020), and acoustic experience (Kapfer et al, 2002).…”

“…Often observed is a developmental drop in input resistance (Magnusson et al, 2005;Scott et al, 2005;Chirila et al, 2007;Hoffpauir et al, 2010;Rusu and Borst, 2011;Franzen et al, 2015Franzen et al, , 2020 based on the upregulation of ion channels (Scott et al, 2005;Hassfurth et al, 2009;Khurana et al, 2012;Franzen et al, 2015). In this developmental period synaptic current accelerates by changes in AMPA receptors (Bellingham et al, 1998;Taschenberger and von Gersdorff, 2000;Joshi and Wang, 2002;Koike-Tani et al, 2005;Youssoufian et al, 2005;Ammer et al, 2012;Felix and Magnusson, 2016;Baumann and Koch, 2017;Franzen et al, 2020) and a reduction or loss of synaptic NMDA receptors (Bellingham et al, 1998;Steinert et al, 2010;Case et al, 2011;Hirtz et al, 2011;Ammer et al, 2012;Winters and Golding, 2018;Franzen et al, 2020). The neuronal morphology remodels by changes in the dendritic arbor (Sanes et al, 1992;Rietzel and Friauf, 1998;Rautenberg et al, 2009) and somatic size (Franzen et al, 2015).…”

“…The neuronal morphology remodels by changes in the dendritic arbor (Sanes et al, 1992;Rietzel and Friauf, 1998;Rautenberg et al, 2009) and somatic size (Franzen et al, 2015). Moreover, the axonal structure refines leading to fewer but often larger synaptic contact sites (Kim and Kandler, 2003;Werthat et al, 2008;Franzen et al, 2020). It is assumed that these developmental processes orchestrate the increase in temporal precision of neuronal input-output functions, a key feature in the auditory brainstem.…”