Role for the Lateral Olivocochlear Neurons in Auditory Function. Focus on “Selective Removal of Lateral Olivocochlear Efferents Increases Vulnerability to Acute Acoustic Injury”

In a paper published in this issue of Journal of Neurophysiology (p. 1775–1785), Darrow and colleagues report that lesions of the lateral superior olive, where the lateral olivocochlear (LOC) efferent originate, enhance auditory evoked potentials in mice. The report also shows that noise-traumatized mouse ears without LOC input are more susceptible to noiseinduced trauma than contralateral ears with intact LOC innervation. The current results contrast with those of previous studies on guinea pigs, chinchillas, and cats that revealed lesion-induced depression of auditory nerve activity. Species differences in LOC transmitter co-localization and release likely underlie these divergent results and reveal LOC function to be even more diverse than previously thought. The function of the LOC efferent neurons is a long-standing mystery; the findings described by Liberman and colleagues in this issue are an exciting step toward identification of a functional role for the LOC system. The LOC efferent pathway originates in and around the lateral superior olive (LSO) and projects to the cochlea. There the LOC neurons terminate on the type I auditory nerve peripheral processes postsynaptic to the inner hair cell/ auditory nerve synapse (for reviews, see Warr 1992; Warr et al. 1986). LOC efferent neurons are thus strategically placed to provide a powerful and dynamic regulation of auditory nerve activity, including the regulation of noise-induced hearing loss. Immunocytochemical labeling studies reveal the LOC neurons contain both excitatory and inhibitory neurotransmitters and neuromodulating peptides, including acetylcholine (ACh), dopamine (DA), dynorphin, enkephalin, -aminobutyric acid (GABA), and calcitonin-gene-related-peptide (CGRP) (for reviews, see Eybalin 1993; Le Prell et al. 2001a; Puel 1995). This chemical richness provides significant potential for either upor downregulation of auditory nerve activity (for one model, see Le Prell et al. 2003a). Darrow and colleagues report that LSO lesions in mice enhance auditory evoked potential amplitude, a result that suggests the net effect of the intact LOC innervation is to downregulate auditory nerve activity (Darrow et al. 2007). In this same report, noise-traumatized mouse ears that lack LOC input are described as more susceptible to noise-induced trauma than contralateral ears with intact LOC innervation. The current results directly contrast with previous studies in other rodent species (reviewed in the following text) and suggest a diversity of roles for the LOC and thus multiple challenges for future investigations. The earliest “lesions” of the LOC system were knife cuts of the olivocochlear bundle (OCB) in cats (Liberman 1990) and chinchillas (Zheng et al. 1999). Both studies suggested the possibility of an excitatory LOC influence on the AN, although neither provided definitive evidence as these cuts disrupted both lateral and medial OC (MOC) pathways, which travel together in the OCB. Spontaneous auditory nerve firing rates were reduced in both studies; driven responses were reduced in lesioned chinchillas but not lesioned cats. Differences in species, anesthesia, and postlesion survival duration all provided potential explanations for differences in the pattern of results. A more selective LSO lesion technique was developed to try and resolve the discrepancies between the early studies and confirm the extent to which LOC neurons modulate auditory nerve activity in the absence of MOC disruptions (Le Prell et al. 2003b). In the guinea pig, LSO lesions produced depressed auditoryevoked potential amplitudes, indicating that the net effect of the intact LOC system was excitatory (Le Prell et al. 2003b). Liberman and colleagues observed the opposite effect in mice (Darrow et al. 2007). Clearly, species differences provide one potential explanation. Differences in the balance of excitatory/ inhibitory LOC transmitter production, localization, and/or release provide likely mechanisms for species differences in LOC function. LOC transmitter colocalization has been well described with many studies using guinea pigs as subjects. For example, double-labeling studies have shown that LSO cell bodies colocalize enkephalin and dynorphin (Abou-Madi et al. 1987; Altschuler et al. 1988), enkephalin and ACh (Altschuler et al. 1983), enkephalin and choline acetyltransferase (ChAT: the enzyme responsible for synthesizing ACh) (Altschuler et al. 1984), or dynorphin and ChAT (Abou-Madi et al. 1987). Other studies have shown colocalization of enkephalin and CGRP (Tohyama et al. 1990) or enkephalin, ACh, and CGRP (Safieddine and Eybalin 1992). Finally, extensive colocalization has been observed with double and triple immunolabeling for ChAT and glutamate decarboxylase (GAD, the enzyme that decarboxylates glutamate to make GABA), tyrosine hydroxylase (TH, the enzyme responsible for catalyzing the conversion of L-tyrosine to the DA precursor dihydroxyphenylalanine), enkephalin, or CGRP, resulting in the conclusion that 90% of the ChAT-positive LSO neurons are also GAD and TH positive, or GAD and enkephalin positive (Safieddine et al. 1997). These results contrast with an early characterization of rat LSO neurons as chemically distinct subpopulations that are either