Principal neuron diversity in the murine lateral superior olive supports multiple sound localization strategies and segregation of information in higher processing centers

Abstract

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.

Molecular and functional profiling of cell diversity and identity in the lateral superior olive, an auditory brainstem center with ascending and descending projections

“…In contrast, Sustained neurons increased their firing rate linearly, whereas Delayed neurons peaked and declined thereafter. These findings are in accordance with previous studies on pLSOs and LOCs in gerbils ( Sanes, 1990 ; Walcher et al, 2011 ), rats ( Kandler and Friauf, 1995 ; Fujino et al, 1997 ; Adam et al, 1999 , 2001 ), and mice ( Sterenborg et al, 2010 ; Walcher et al, 2011 ; Haragopal and Winters, 2023 ). Therefore, they provide independent physiological evidence that cluster 1 consists of pLSOs whereas cluster 2 is composed of LOCs.…”

“…Our patch-seq results for genes expressing vGLUT confirm in situ hybridization results showing the absence of vGLUT1 and the presence of vGLUT2 in mouse LSO somata (Ito et al, 2011). They are also consistent with the detection of vGLUT2 in the LSO of rat, mouse, and owl monkey at the protein level (Blaesse et al, 2005;Haragopal and Winters, 2023) and at the mRNA level (Hackett et al, 2011). The association of vGLUT2 with pLSOs is consistent with findings in rats that vGLUT2-positive LSO neurons project into the contralateral inferior colliculus (IC; virtually no ipsilateral projection), thus representing ascending neurons (Ito and Oliver, 2010).…”

“…Reportedly, membrane properties of excitatory pLSOs favor integrative level coding, whereas those of inhibitory pLSOs favor time coding (Haragopal and Winters, 2023).…”

“…Two subpopulations of pLSOs can be distinguished by their intrinsic firing pattern in vitro (rats: Barnes-Davies et al, 2004 ). In mice, the first subtype, termed single spiking ( Sterenborg et al, 2010 ) or onset-burst pLSOs ( Haragopal and Winters, 2023 ), fires 1–5 action potentials (APs) of short latency during prolonged depolarization. The second pLSO subtype fires throughout the duration of the stimulus and has been termed multiple firing ( Sterenborg et al, 2010 ) or multi-spiking ( Haragopal and Winters, 2023 ).…”

Tonotopic distribution and inferior colliculus projection pattern of inhibitory and excitatory cell types in the lateral superior olive of mice

“…This configuration gives LSO PNs intrinsic sensitivity to interaural level and timing. Although their level sensitivity has been emphasized for some time, their timing functions are increasingly being examined (Franken et al., 2018; Haragopal & Winters, 2023; Joris & Trussell, 2018).…”