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Perisomatic voltage-gated sodium channels actively maintain linear synaptic integration in principal neurons of the medial superior olive.

ABSTRACT: Principal neurons of the medial superior olive (MSO) compute azimuthal sound location by integrating phase-locked inputs from each ear. While previous experimental and modeling studies have proposed that voltage-gated sodium channels (VGSCs) play an important role in synaptic integration in the MSO, these studies appear at odds with the unusually weak active backpropagation of action potentials into the soma and dendrites. To understand the spatial localization and biophysical properties of VGSCs, we isolated sodium currents in MSO principal neurons in gerbil brainstem slices. Nucleated and cell-attached patches revealed that VGSC density at the soma is comparable to that of many other neuron types, but channel expression is largely absent from the dendrites. Further, while somatic VGSCs activated with conventional voltage dependence (V(1/2) = -30 mV), they exhibited an unusually negative range of steady-state inactivation (V(1/2) = -77 mV), leaving approximately 92% of VGSCs inactivated at the resting potential (approximately -58 mV). In current-clamp experiments, non-inactivated VGSCs were sufficient to amplify subthreshold EPSPs near action potential threshold, counterbalancing the suppression of EPSP peaks by low voltage-activated potassium channels. EPSP amplification was restricted to the perisomatic region of the neuron, and relatively insensitive to preceding inhibition. Finally, computational modeling showed that the exclusion of VGSCs from the dendrites equalizes somatic EPSP amplification across synaptic locations and lowered the threshold for bilateral versus unilateral excitatory synaptic inputs. Together, these findings suggest that the pattern of sodium channel expression in MSO neurons contributes to these neurons' selectivity for coincident binaural inputs.

SUBMITTER: Scott LL

PROVIDER: S-EPMC2827923 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Perisomatic voltage-gated sodium channels actively maintain linear synaptic integration in principal neurons of the medial superior olive.

Scott Luisa L LL Mathews Paul J PJ Golding Nace L NL

The Journal of neuroscience : the official journal of the Society for Neuroscience 20100201 6

Principal neurons of the medial superior olive (MSO) compute azimuthal sound location by integrating phase-locked inputs from each ear. While previous experimental and modeling studies have proposed that voltage-gated sodium channels (VGSCs) play an important role in synaptic integration in the MSO, these studies appear at odds with the unusually weak active backpropagation of action potentials into the soma and dendrites. To understand the spatial localization and biophysical properties of VGSC ...[more]

PMID: 20147532

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Project description: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.

Project description:Principal neurons (PNs) of the lateral superior olive nucleus (LSO) in the brainstem of mammals compare information between the two ears and enable sound localization on the horizontal plane. The classical view of the LSO is that it extracts ongoing interaural level differences (ILDs). Although it has been known for some time that LSO PNs have intrinsic relative timing sensitivity, recent reports further challenge conventional thinking, suggesting the major function of the LSO is detection of interaural time differences (ITDs). LSO PNs include inhibitory (glycinergic) and excitatory (glutamatergic) neurons which differ in their projection patterns to higher processing centers. Despite these distinctions, intrinsic property differences between LSO PN types have not been explored. The intrinsic cellular properties of LSO PNs are fundamental to how they process and encode information, and ILD/ITD extraction places disparate demands on neuronal properties. Here we examine the ex vivo electrophysiology and cell morphology of inhibitory and excitatory LSO PNs in mice. Although overlapping, properties of inhibitory LSO PNs favor time coding functions while those of excitatory LSO PNs favor integrative level coding. Inhibitory and excitatory LSO PNs exhibit different activation thresholds, potentially providing further means to segregate information in higher processing centers. Near activation threshold, which may be physiologically similar to the sensitive transition point in sound source location for LSO, all LSO PNs exhibit single-spike onset responses that can provide optimal time encoding ability. As stimulus intensity increases, LSO PN firing patterns diverge into onset-burst cells, which can continue to encode timing effectively regardless of stimulus duration, and multi-spiking cells, which can provide robust individually integrable level information. This bimodal response pattern may produce a multi-functional LSO which can encode timing with maximum sensitivity and respond effectively to a wide range of sound durations and relative levels.

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Perisomatic voltage-gated sodium channels actively maintain linear synaptic integration in principal neurons of the medial superior olive.

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Perisomatic voltage-gated sodium channels actively maintain linear synaptic integration in principal neurons of the medial superior olive.

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