Research paper
Cytoarchitecture of the human superior olivary complex: Nuclei of the trapezoid body and posterior tier

https://doi.org/10.1016/j.heares.2008.04.010Get rights and content

Abstract

The superior olivary complex (SOC) is a cluster of nuclei situated in the caudal brainstem tegmentum that forms an essential component of the auditory pathway. The SOC includes two principal nuclei, the medial and lateral superior olives (MSO and LSO respectively), that have clear roles in sound source localization. Surrounding the principal nuclei are a number of periolivary nuclei (PON) that vary significantly between mammalian species but function in multiple aspects of hearing. Although the PON have been studied in numerous laboratory animals, these nuclei have not been delineated in human. The major goal of this study is to, based on myeloarchitecture, location, neuronal morphology and cytoarchitecture, define the PON within the human SOC and provide estimates of neuronal number within these nuclei. Results from the study of twelve human brainstems provide evidence for six morphologically distinct cell groups: three within the trapezoid body and three along the posterior aspect of the SOC. Based on the analysis of human tissue stained for myelin, Nissl substance, or impregnated with silver, the human PON appear largely homologous to the PON described in other low-frequency hearing animals.

Introduction

The superior olivary complex (SOC) is a constellation of nuclei within the lower brainstem tegmentum that functions in numerous capacities, including localization of sound sources, encoding temporal features of sounds and descending modulation of the cochlear nucleus and cochlea (see reviews by Heffner and Masterton, 1990, Spangler and Warr, 1991, Schwartz, 1992, Thompson and Schofield, 2000, Oliver, 2000). The human SOC extends from the rostral medulla oblongata to the mid-pons, directly anterior and medial to the facial nucleus, between the inferior olive and trigeminal motor nucleus (Moore and Moore, 1971, Strominger and Hurwitz, 1976, Kulesza, 2007). The human SOC includes two principal nuclei, the medial superior olive (MSO) and the lateral superior olive (LSO), both of which are structurally similar to the corresponding nuclei in other mammals and can be distinguished based on location, cell body morphology and cytoarchitecture (Moore and Moore, 1971, Strominger and Hurwitz, 1976, Kulesza, 2007). Notably, the MSO and LSO include neurons with dendrites arranged in a laminar fashion indicative of the tonotopic axis described for these nuclei in other species (Guinan et al., 1972, Schwartz, 1977, Cant, 1984, Kulesza, 2007).

The MSO and LSO are flanked by a number of accessory or periolivary nuclei (PON) that vary dramatically between species in size (neuronal number and volume), connectivity and even function. These PON, as a group, receive input from numerous auditory and non-auditory regions and project widely over the neuroaxis (Edwards et al., 1979, Oliver, 2000, Shore et al., 2000, Thompson and Schofield, 2000, Schofield, 2002, Coomes and Schofield, 2004, Coomes Peterson and Schofield, 2007). It has been demonstrated by numerous authors that the periolivary cell groups, especially the nuclei of the trapezoid body (medial = MNTB, ventral = VNTB, lateral = LNTB) and the superior paraolivary nucleus (SPON) release mainly inhibitory neurotransmitters (i.e. GABA and glycine; Roberts and Ribak, 1987, Helfert et al., 1989, Kulesza and Berrebi, 2000). Additionally, the PON contain a significant population of cholinergic neurons (Osen and Roth, 1969, Warr, 1975, Tago et al., 1989, Vetter et al., 1991, Lauterborn et al., 1993). These findings, taken together indicate that the PON have a broad influence over the auditory system, function in multiple aspects of hearing and may influence other sensory and even motor pathways.

There are few details available in the literature regarding the human SOC outside of the MSO and LSO. Consistently, the human PON have been treated as a large, indistinct and sparsely populated region surrounding the MSO and LSO. Further, the terminology used for the human PON has been inconsistent and has varied from schemes used for laboratory animals (Moore et al., 1999, Bazwinsky et al., 2003). However, two significant points have emerged regarding the human PON. First, there is immunocytochemical evidence from an intriguing developmental study that at least some of the neurons surrounding the MSO and LSO are cholinergic (Moore et al., 1999). Secondly, there is a discrepancy regarding the existence of the MNTB in the human brainstem. The MNTB is a group of glycinergic neurons situated within the fibers of the trapezoid body and receives large, secure synapses from the contralateral cochlear nucleus via the calyx of Held (Harrison and Warr, 1962, Lenn and Reese, 1966, Helfert et al., 1989, Helfert and Aschoff, 1997). The neurons of the MNTB play an essential role in sound source localization by providing fast and precisely timed inhibition to the LSO and MSO (Grothe, 1994, Brand et al., 2002). Numerous authors, in their study of the human brainstem, have failed to find structural evidence for an MNTB (Moore and Moore, 1971, Strominger and Hurwitz, 1976, Moore, 1987, Moore, 2000, Bazwinsky et al., 2003). Interestingly, other authors find a rudimentary nucleus (Richter et al., 1983, Glendenning and Masterton, 1998). The absence of a MNTB in humans would truly be significant, as it would negate current models of sound source localization for the human auditory system. Thus, a major objective of this investigation is to provide structural evidence for the existence of the MNTB in the human brainstem.

Based on the drastic interspecies variability observed in the SOC (Glendenning and Masterton, 1998) and human’s relatively narrow hearing range and complex repertoire of vocalizations, we should expect significant modifications in the arrangement of the SOC, even from other low-frequency hearing mammals (gerbil and rhesus; Moore and Moore, 1971, Nordeen et al., 1983, Bazwinsky et al., 2005). Further, it should be a priority to establish the structural organization of the human auditory brainstem in an effort to more accurately extend findings from animal studies to human auditory function. A detailed quantitative analysis of the organization of the human auditory brainstem will be essential for our understanding of the comparative anatomy of the SOC and will provide the foundation necessary to clarify the functional role of the SOC in human hearing. To this end, the goal of this paper is to establish the organization of the human SOC, specifically the PON, and provide a quantitative analysis of the structural features of these cell groups.

Section snippets

General

This description of the cytoarchitecture of the human PON is based on results from a variety of techniques namely, staining of Nissl substance with Giemsa or neutral red, staining of myelin sheaths with Luxol Fast Blue and modified silver staining to reveal cell body and dendritic architecture. The classification for the PON used herein is derived from schemes and terminology devised by Schofield and Cant (1991) and Kulesza et al. (2002) using the criteria of location within the brainstem, cell

General observations

Progressing from caudal to rostral through the human brainstem, the SOC begins in the rostral medulla oblongata and extends for over 6 mm into the mid-pons. The PON can be traced rostrally for approximately 5.4 mm where they become indistinguishable and blend with the loosely organized rostral periolivary region (RPO; Paxinos and Huang, 1995, Kulesza, 2007). In the human SOC, six distinct nuclei can be identified surrounding the MSO and LSO. Fig. 1 shows a schematic of the SOC nuclei over their

General comments

This is the first comprehensive report concerning the human SOC cell groups outside of the principal nuclei. Based on myelin staining patterns, location, neuronal morphology and cytoarchitecture, six distinct nuclei can be designated in the human SOC outside of the MSO and LSO. This report provides the first detailed descriptions and quantification of neuronal number within these nuclei. This report taken together with previous work on the human MSO and LSO (Kulesza, 2007), indicates that the

Summary, limitations and future directions

This paper provides evidence for six distinct cell groups surrounding the MSO and LSO in the human SOC based on location, cell body morphology and cytoarchitecture. In terms of general morphology, the human PON are similar to what has been described for the corresponding cell groups in laboratory mammals. However, the descriptions of the human SOC in the paper are based on material processed by routine, non-specific histological methods. These methods provide only structural information of the

Acknowledgements

This work was supported by the LECOM Research Collective and a grant from the Deafness Research Foundation. The author would like to thank Jack Caldwell for review of an earlier version of this manuscript and Ron Brandon Trale for technical assistance.

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