Physiological Diversity Influences Detection of Stimulus Envelope and Fine Structure in Neurons of the Medial Superior Olive

Abstract

The neurons of the medial superior olive (MSO) of mammals extract azimuthal information from the delays between sounds reaching the two ears [interaural time differences (ITDs)]. Traditionally, all models of sound localization have assumed that MSO neurons represent a single population of cells with specialized and homogeneous intrinsic and synaptic properties that enable the detection of synaptic coincidence on a timescale of tens to hundreds of microseconds. Here, using patch-clamp recordings from large populations of anatomically labeled neurons in brainstem slices from male and female Mongolian gerbils (Meriones unguiculatus), we show that MSO neurons are far more physiologically diverse than previously appreciated, with properties that depend regionally on cell position along the topographic map of frequency. Despite exhibiting a similar morphology, neurons in the MSO exhibit subthreshold oscillations of differing magnitudes that drive action potentials at rates between 100 and 800 Hz. These oscillations are driven primarily by voltage-gated sodium channels and are distinct from resonant properties derived from other active membrane properties. We show that graded differences in these and other physiological properties across the MSO neuron population enable the MSO to duplex the encoding of ITD information in both fast, submillisecond time-varying signals as well as in slower envelopes.

SIGNIFICANCE STATEMENT Neurons in the medial superior olive (MSO) encode sound localization cues by detecting microsecond differences in the arrival times of inputs from the left and right ears, and it has been assumed that this computation is made possible by highly stereotyped structural and physiological specializations. Here we report using a large (>400) sample size in which MSO neurons show a strikingly large continuum of functional properties despite exhibiting similar morphologies. We demonstrate that subthreshold oscillations mediated by voltage-gated Na⁺ channels play a key role in conferring graded differences in firing properties. This functional diversity likely confers capabilities of processing both fast, submillisecond-scale synaptic activity (acoustic “fine structure”), and slow-rising envelope information that is found in amplitude-modulated sounds and speech patterns.