Synapses on human spiral ganglion cells : a transmission electron microscopy and immunohistochemical study Helge Rask-Andersen a; *, Sven Tylstedt a , Anders Kinnefors a , R.-B. Illing b a Department of Otolaryngology, University Hospital (Akademiska sjukhuset) of Uppsala, 751 85 Uppsala, Sweden b Neurobiological Research Laboratory, Department of Otorhinolaryngology, University of Freiburg, 79106 Freiburg, Germany Received 25 March 1999; received in revised form 4 August 1999; accepted 14 September 1999 Abstract A transmission electron microscopy (TEM) study and synaptophysin immunoreactivity analysis of neurons in the human spiral ganglion was performed with particular emphasis on the demonstration of synapses. The study was based on surgical biopsy material obtained during transcochlear meningioma surgery. Vesiculated nerve endings of unmyelinated nerve fibers occurred frequently on the small ganglion cells at all levels. The nerve terminals exhibited abundant clear synaptic vesicles but also dense-core vesicles. Multisynaptic contact sites were also seen with fibers of the intraganglionic spiral bundle (IGSB). Complex associations of synapses could be demonstrated, including several synaptic terminals in conjunction with contact sites or an adherent type of junctions on large ganglion cells. These contact sites exhibited membrane densities which were symmetric or asymmetric, changed their polarity recurrently over their extension from one cell to the other and back and lacked clear synaptic vesicles. This suggests the existence of connections between efferents, belonging to the olivocochlear bundle, and both small and large ganglion cells. Thus, both the inner and outer hair cell system may be under the influence of efferent innervation in the human spiral ganglion. The morphology and course of synaptophysin-positive nerve fibers indicated that synaptic contacts within the spiral ganglion, as observed under the electron microscope, may be abundant. These results indicate that complex neural processing may occur at the level of the spiral ganglion in man. ß 2000 Elsevier Science B.V. All rights reserved. Key words: Spiral ganglion ; Inner ear ; Electron microscopy ; Synaptophysin ; Human 1. Introduction The inner ear contains two parallel sensory auditory subsystems: the inner and outer hair cell systems (IHC and OHC, respectively), consisting of two di¡erent af- ferent neurons within the spiral ganglion, type I and type II, and small lateral and the large medial e¡erent ¢bers of olivocochlear neurons projecting to the IHC and the OHC subsystems, respectively. Ultrastructural studies of the human spiral ganglion suggest that there exist fundamental anatomical di¡erences when com- pared to data available from animals studied (Kimura et al., 1979; Ota and Kimura, 1980; Arnold, 1987; Rask-Andersen et al., 1997; Tylstedt et al., 1997). For instance, the human spiral ganglion contains distin- guishable populations of neurons represented by small and large cells which generally lack a compact myelin layer. It is not known with certainty whether these cells correspond to the type I and type II cells described in animals (Spoendlin, 1972). En passent, synapses and axo-somatic contacts have been observed in the spiral ganglion of adult primates (Kimura et al., 1979; Kimura et al., 1987; Nadol, 1988) as well as in the newborn human (Arnold, 1982). These synapses have been thought to represent e¡erent con- nections with the olivocochlear ¢bers of the intragan- glionic spiral bundle (IGSB). In small rodents, Retzius (1895) found unmyelinated spiral ganglion cells that were often multipolar. Based on ultrastructural and his- tochemical grounds, Ross and Burkel (1973) believed them to be autonomic, post-ganglionic (parasympa- thetic) neurons. Synaptic sites on neurons were found 0378-5955 / 00 / $ ^ see front matter ß 2000 Elsevier Science B.V. All rights reserved. PII:S0378-5955(99)00179-3 * Corresponding author. Tel.: +46 (18) 665303; Fax: +46 (18) 665314; E-mail: helge.rask.andersen@ent.uas.lul.se Hearing Research 141 (2000) 1^11 www.elsevier.com/locate/heares