Lateral Olivocochlear Neurons Research Articles

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

The lateral superior olive (LSO), a prominent integration center in the auditory brainstem, contains a remarkably heterogeneous population of neurons. Ascending neurons, predominantly principal neurons (pLSOs), process interaural level differences for sound localization. Descending neurons (lateral olivocochlear neurons, LOCs) provide feedback into the cochlea and are thought to protect against acoustic overload. The molecular determinants of the neuronal diversity in the LSO are largely unknown. Here, we used patch-seq analysis in mice at postnatal days P10-12 to classify developing LSO neurons according to their functional and molecular profiles. Across the entire sample (n = 86 neurons), genes involved in ATP synthesis were particularly highly expressed, confirming the energy expenditure of auditory neurons. Two clusters were identified, pLSOs and LOCs. They were distinguished by 353 differentially expressed genes (DEGs), most of which were novel for the LSO. Electrophysiological analysis confirmed the transcriptomic clustering. We focused on genes affecting neuronal input–output properties and validated some of them by immunohistochemistry, electrophysiology, and pharmacology. These genes encode proteins such as osteopontin, Kv11.3, and Kvβ3 (pLSO-specific), calcitonin-gene-related peptide (LOC-specific), or Kv7.2 and Kv7.3 (no DEGs). We identified 12 “Super DEGs” and 12 genes showing “Cluster similarity.” Collectively, we provide fundamental and comprehensive insights into the molecular composition of individual ascending and descending neurons in the juvenile auditory brainstem and how this may relate to their specific functions, including developmental aspects.

Electrical signaling in cochlear efferents is driven by an intrinsic neuronal oscillator

Efferent neurons are believed to play essential roles in maintaining auditory function. The lateral olivocochlear (LOC) neurons-which project from the brainstem to the inner ear, where they release multiple transmitters including peptides, catecholamines, and acetylcholine-are the most numerous yet least understood elements of efferent control of the cochlea. Using invitro calcium imaging and patch-clamp recordings, we found that LOC neurons in juvenile and young adult mice exhibited extremely slow waves of activity (∼0.1 Hz). These seconds-long bursts of Na+ spikes were driven by an intrinsic oscillator dependent on L-type Ca2+ channels and were not observed in prehearing mice, suggesting an age-dependent mechanism underlying the intrinsic oscillator. Using optogenetic approaches, we identified both ascending (T-stellate cells of the cochlear nucleus) and descending (auditory cortex) sources of synaptic excitation, as well as the synaptic receptors used for such excitation. Additionally, we identified potent inhibition originating in the glycinergic medial nucleus of trapezoid body (MNTB). Conductance-clamp experiments revealed an unusual mechanism of electrical signaling in LOC neurons, in which synaptic excitation and inhibition served to switch on and off the intrinsically generated spike burst mechanism, allowing for prolonged periods of activity or silence controlled by brief synaptic events. Protracted bursts of action potentials may be essential for effective exocytosis of the diverse transmitters released by LOC fibers in the cochlea.

Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity.

Calcitonin-gene-related peptide (CGRP) is a lateral olivocochlear (LOC) efferent neurotransmitter. Depression of sound-driven auditory brainstem response amplitude in CGRP-null mice suggests the potential for endogenous CGRP release to upregulate spontaneous and/or sound-driven auditory nerve (AN) activity. We chronically infused CGRP into the guinea pig cochlea and evaluated changes in AN activity as well as outer hair cell (OHC) function. The amplitude of both round window noise (a measure of ensemble spontaneous activity) and the synchronous whole-nerve response to sound (compound action potential, CAP) were enhanced. Lack of change in both onset adaptation and steady state amplitude of sound-evoked distortion product otoacoustic emission (DPOAE) responses indicated CGRP had no effect on OHCs, suggesting the origin of the observed changes was neural. Combined with results from the CGRP-null mice, these results appear to confirm that endogenous CGRP enhances auditory nerve activity when released by the LOC neurons. However, infusion of the CGRP receptor antagonist CGRP (8–37) did not reliably influence spontaneous or sound-driven AN activity, or OHC function, results that contrast with the decreased ABR amplitude measured in CGRP-null mice.

Sound exposure dynamically induces dopamine synthesis in cholinergic LOC efferents for feedback to auditory nerve fibers.

Lateral olivocochlear (LOC) efferent neurons modulate auditory nerve fiber (ANF) activity using a large repertoire of neurotransmitters, including dopamine (DA) and acetylcholine (ACh). Little is known about how individual neurotransmitter systems are differentially utilized in response to the ever-changing acoustic environment. Here we present quantitative evidence in rodents that the dopaminergic LOC input to ANFs is dynamically regulated according to the animal's recent acoustic experience. Sound exposure upregulates tyrosine hydroxylase, an enzyme responsible for dopamine synthesis, in cholinergic LOC intrinsic neurons, suggesting that individual LOC neurons might at times co-release ACh and DA. We further demonstrate that dopamine down-regulates ANF firing rates by reducing both the hair cell release rate and the size of synaptic events. Collectively, our results suggest that LOC intrinsic neurons can undergo on-demand neurotransmitter re-specification to re-calibrate ANF activity, adjust the gain at hair cell/ANF synapses, and possibly to protect these synapses from noise damage.

Efferent Inhibition of the Cochlea.

Cholinergic efferent neurons originating in the brainstem innervate the acoustico-lateralis organs (inner ear, lateral line) of vertebrates. These release acetylcholine (ACh) to inhibit hair cells through activation of calcium-dependent potassium channels. In the mammalian cochlea, ACh shunts and suppresses outer hair cell (OHC) electromotility, reducing the essential amplification of basilar membrane motion. Consequently, medial olivocochlear neurons that inhibit OHCs reduce the sensitivity and frequency selectivity of afferent neurons driven by cochlear vibration of inner hair cells (IHCs). The cholinergic synapse on hair cells involves an unusual ionotropic ACh receptor, and a near-membrane postsynaptic cistern. Lateral olivocochlear (LOC) neurons modulate type I afferents by still-to-be-defined synaptic mechanisms. Olivocochlear neurons can be activated by a reflex arc that includes the auditory nerve and projections from the cochlear nucleus. They are also subject to modulation by higher-order central auditory interneurons. Through its actions on cochlear hair cells, afferent neurons, and higher centers, the olivocochlear system protects against age-related and noise-induced hearing loss, improves signal coding in noise under certain conditions, modulates selective attention to sensory stimuli, and influences sound localization.

Restricted loss of olivocochlear but not vestibular efferent neurons in the senescent gerbil (Meriones unguiculatus).

Degeneration of hearing and vertigo are symptoms of age-related auditory and vestibular disorders reflecting multifactorial changes in the peripheral and central nervous system whose interplay remains largely unknown. Originating bilaterally in the brain stem, vestibular and auditory efferent cholinergic projections exert feedback control on the peripheral sensory organs, and modulate sensory processing. We studied age-related changes in the auditory and vestibular efferent systems by evaluating number of cholinergic efferent neurons in young adult and aged gerbils, and in cholinergic trigeminal neurons serving as a control for efferents not related to the inner ear. We observed a significant loss of olivocochlear (OC) neurons in aged compared to young adult animals, whereas the overall number of lateral superior olive (LSO) cells was not reduced in aging. Although the loss of lateral and medial olivocochlear (MOC) neurons was uniform and equal on both sides of the brain, there were frequency-related differences within the lateral olivocochlear (LOC) neurons, where the decline was larger in the medial limb of the superior olivary nucleus (high frequency representation) than in the lateral limb (middle-to-low frequency representation). In contrast, neither the number of vestibular efferent neurons, nor the population of motor trigeminal neurons were significantly reduced in the aged animals. These observations suggest differential effects of aging on the respective cholinergic efferent brainstem systems.

The olivocochlear reflex strength and cochlear sensitivity are independently modulated by auditory cortex microstimulation.

In mammals, efferent projections to the cochlear receptor are constituted by olivocochlear (OC) fibers that originate in the superior olivary complex. Medial and lateral OC neurons make synapses with outer hair cells and with auditory nerve fibers, respectively. In addition to the OC system, there are also descending projections from the auditory cortex that are directed towards the thalamus, inferior colliculus, cochlear nucleus, and superior olivary complex. Olivocochlear function can be assessed by measuring a brainstem reflex mediated by auditory nerve fibers, cochlear nucleus neurons, and OC fibers. Although it is known that the OC reflex is activated by contralateral acoustic stimulation and produces a suppression of cochlear responses, the influence of cortical descending pathways in the OC reflex is largely unknown. Here, we used auditory cortex electrical microstimulation in chinchillas to study a possible cortical modulation of cochlear and auditory nerve responses to tones in the absence and presence of contralateral noise. We found that cortical microstimulation produces two different peripheral modulations: (i) changes in cochlear sensitivity evidenced by amplitude modulation of cochlear microphonics and auditory nerve compound action potentials and (ii) enhancement or suppression of the OC reflex strength as measured by auditory nerve responses, which depended on the intersubject variability of the OC reflex. Moreover, both corticofugal effects were not correlated, suggesting the presence of two functionally different efferent pathways. These results demonstrate that auditory cortex electrical microstimulation independently modulates the OC reflex strength and cochlear sensitivity.

Disruption of lateral olivocochlear neurons with a dopaminergic neurotoxin depresses spontaneous auditory nerve activity

Neurons of the lateral olivocochlear (LOC) system project from the auditory brainstem to the cochlea, where they synapse on radial dendrites of auditory nerve fibers. Selective LOC disruption depresses sound-evoked auditory nerve activity in the guinea pig, but enhances it in the mouse. Here, LOC disruption depressed spontaneous auditory nerve activity in the guinea pig. Recordings from single auditory nerve fibers revealed a significantly reduced proportion of fibers with the highest spontaneous firing rates (SRs) and an increased proportion of neurons with lower SRs. Ensemble activity, estimated using round window noise, also decreased after LOC disruption. Decreased spontaneous activity after LOC disruption may be a consequence of reduced tonic release of excitatory transmitters from the LOC terminals in guinea pigs.

Physiological characterization of vestibular efferent brainstem neurons using a transgenic mouse model.

The functional role of efferent innervation of the vestibular end-organs in the inner ear remains elusive. This study provides the first physiological characterization of the cholinergic vestibular efferent (VE) neurons in the brainstem by utilizing a transgenic mouse model, expressing eGFP under a choline-acetyltransferase (ChAT)-locus spanning promoter in combination with targeted patch clamp recordings. The intrinsic electrical properties of the eGFP-positive VE neurons were compared to the properties of the lateral olivocochlear (LOC) brainstem neurons, which gives rise to efferent innervation of the cochlea. Both VE and the LOC neurons were marked by their negative resting membrane potential <−75 mV and their passive responses in the hyperpolarizing range. In contrast, the response properties of VE and LOC neurons differed significantly in the depolarizing range. When injected with positive currents, VE neurons fired action potentials faithfully to the onset of depolarization followed by sparse firing with long inter-spike intervals. This response gave rise to a low response gain. The LOC neurons, conversely, responded with a characteristic delayed tonic firing upon depolarizing stimuli, giving rise to higher response gain than the VE neurons. Depolarization triggered large TEA insensitive outward currents with fast inactivation kinetics, indicating A-type potassium currents, in both the inner ear-projecting neuronal types. Immunohistochemistry confirmed expression of Kv4.3 and 4.2 ion channel subunits in both the VE and LOC neurons. The difference in spiking responses to depolarization is related to a two-fold impact of these transient outward currents on somatic integration in the LOC neurons compared to in VE neurons. It is speculated that the physiological properties of the VE neurons might be compatible with a wide-spread control over motion and gravity sensation in the inner ear, providing likewise feed-back amplification of abrupt and strong phasic signals from the semi-circular canals and of tonic signals from the gravito-sensitive macular organs.

Dynorphin release by the lateral olivocochlear efferents may inhibit auditory nerve activity: A cochlear drug delivery study

Dynorphin (dyn) is suggested to excite the auditory nerve (AN) when released by the lateral olivocochlear (LOC) efferents. However, previous studies evaluated either intravenously delivered dyn-like agents, raising the potential for systemic (central) effects, or agent concentrations unlikely to be achieved via endogenous cochlear release. This study tested the hypothesis that biologically relevant increases in dyn levels in the cochlea achieved via diffusion of the drug of (−)pentazocine across the round window membrane enhances AN firing. In general, amplitude of the cochlear whole-nerve action potential (CAP) was depressed following drug application. These results suggest that dyn released by the LOC neurons would likely act as an inhibitory transmitter substance in the LOC system; neurotransmission is one of the LOC system's vast unknowns.

Effects of cochlear ablation on amino acid levels in the rat cochlear nucleus and superior olive

Amino acids have important roles in the chemistry of the auditory system, including communication among neurons. There is much evidence for glutamate as a neurotransmitter from auditory nerve fibers to cochlear nucleus neurons. Previous studies in rodents have examined effects of removal of auditory nerve input by cochlear ablation on levels, uptake and release of glutamate in cochlear nucleus subdivisions, as well as on glutamate receptors. Effects have also been reported on uptake and release of γ-aminobutyrate (GABA) and glycine, two other amino acids strongly implicated in cochlear nucleus synaptic transmission. We mapped the effects of cochlear ablation on the levels of amino acids, including glutamate, GABA, glycine, aspartate, glutamine, taurine, serine, threonine, and arginine, in microscopic subregions of the rat cochlear nucleus. Submicrogram-size samples microdissected from freeze-dried brainstem sections were assayed for amino acid levels by high performance liquid chromatography. After cochlear ablation, glutamate and aspartate levels decreased by 2 days in regions receiving relatively dense innervation from the auditory nerve, whereas the levels of most other amino acids increased. The results are consistent with a close association of glutamate and aspartate with auditory nerve fibers and of other amino acids with other neurons and glia in the cochlear nucleus. A consistent decrease of GABA level in the lateral superior olive could be consistent with a role in some lateral olivocochlear neurons. The results are compared with those obtained with the same methods for the rat vestibular nerve root and nuclei after vestibular ganglionectomy.

Urocortin‐expressing olivocochlear neurons exhibit tonotopic and developmental changes in the auditory brainstem and in the innervation of the cochlea

The mammalian cochlea is under direct control of two groups of cholinergic auditory brainstem neurons, the medial and the lateral olivocochlear neurons. The former modulate the electromechanical amplification in outer hair cells and the latter the transduction of inner hair cells to auditory nerve fibers. The lateral olivocochlear neurons express not only acetylcholine but a variety of co-transmitters including urocortin, which is known to regulate homeostatic responses related to stress; it may also be related to the ontogeny of hearing as well as the generation of hearing disorders. In the present study, we investigated the distribution of urocortin-expressing lateral olivocochlear neurons and their connectivity and distribution of synaptic terminals in the cochlea of juvenile and adult gerbils. In contrast to most other rodents, the gerbil's audiogram covers low frequencies similar to humans, although their communication calls are exclusively in the high-frequency domain. We confirm that in the auditory brainstem urocortin is expressed exclusively in neurons within the lateral superior olive and their synaptic terminals in the cochlea. Moreover, we show that in adult gerbils urocortin expression is restricted to the medial, high-frequency processing, limb of the lateral superior olive and to the mid and basal parts of the cochlea. The same pattern is present in juvenile gerbils shortly before hearing onset (P 9) but transiently disappears after hearing onset, when urocortin is also expressed in low-frequency processing regions. These results suggest a possible role of urocortin in late cochlear development and in the processing of social calls in adult animals.

Lateral olivocochlear (LOC) neurons of the mouse LSO receive excitatory and inhibitory synaptic inputs with slower kinetics than LSO principal neurons

We examined membrane properties and synaptic responses of neurons in the mouse lateral superior olivary nucleus (LSO). Two clear populations were identified consistent with: principal neurons which are involved in detecting interaural intensity differences (IIDs) and efferent neurons of the lateral olivocochlear (LOC) system which project to the cochlea. Principal neurons fired a short latency action potential (AP) often followed by an AP train during maintained depolarization. They possessed sustained outward K + currents, with little or no transient K + current (I A) and a prominent hyperpolarization-activated non-specific cation conductance, I H. On depolarization, LOC neurons exhibited a characteristic delay to the first AP. These neurons possessed a prominent transient outward current I A, but had no I H. Both LOC and principal neurons received glutamatergic and glycinergic synaptic inputs. LOC synaptic responses decayed more slowly than those of principal neurons; the mean decay time constant of AMPA receptor-mediated EPSCs was around 1 ms in principal neurons and 4 ms in LOC neurons. Decay time constants for glycinergic IPSCs were around 5 ms in principal neurons and 10 ms in LOC neurons. We conclude that principal cells receive fast synaptic responses appropriate for integration of IID inputs, while the LOC cells possess excitatory and inhibitory receptors with much slower kinetics.

Projecting from the superior olivary complex to the inner ear in the cat: a retrograde fluorescent labelling study

To investigate the distribution and projective feature of cat olivocochlear neurons. Eleven adult cats were divided into two groups randomly. The experimental group of eight cats was injected of 1% cholera toxin B (CTB) to the left cochlea, while injected of 5% fluoro gold (FG) to the right cochlea. The control group of three cats was injected of saline to bilateral cochlea. After a survival time of 7 days, serial frozen sections were cut in the cat brainstem. All the sections were processed by immunofluorescent procedure for CTB and FG, and the labeled olivocochlear neurons were observed by fluorescent microscope. In the experimental group, the mean total of olivocochlear neurons labeled by CTB and FG was 3210 +/- 168, including lateral olivocochlear neurons (LOC, 2298 +/- 120) and medial olivocochlear neurons (MOC, 913 +/- 64). The labeled neurons were divided into three different types according to their feature of projection: neurons which only projected to the ipsilateral cochlea, neurons which only projected to the contralateral cochlea, and double-labeled neurons which projected both to the ipsilateral and contralateral cochlea, but the double-labeled neurons comprised 3.9% and 15.1% in the LOC and MOC system respectively. No labeled neurons were found in the control group. There are three types of neurons in the cat olivocochlear system. The neurons which projected to the bilateral cochlea may distribute both in the LOC and MOC system.

Environmental enrichment to sound activates dopaminergic pathways in the auditory system

NIU X, TAHERA Y, CANLON B. Environmental enrichment to sound activates dopaminergic pathways in the peripheral and central auditory system. PHYSIOL. BEHAV. 00(0) 000-000, 2006. Environmental enrichment to sound stimulation, in the adult, can promote physiological changes and protection against trauma in the auditory peripheral and central nervous system. Sound enrichment, or sound conditioning is a method that utilizes a low-level, non-damaging acoustic stimulus as a protective agent. Pre-treating subjects to a moderate or low-level acoustic stimulus reduces the damaging effects of a subsequent traumatic stimulus. The intention of this review is to describe how environmental enrichment to sound affords protection against a subsequent trauma, and the role that the dopaminergic pathways in the cochlea and the auditory brainstem play in this protection. Dopamine is released from the lateral efferents and exerts a tonic inhibition of auditory nerve activity thus preserving auditory sensitivity and protecting against excitotoxicity. Sound conditioning up-regulated tyrosine hydroxylase in the lateral efferents under the inner hair cells and acoustic trauma reduced these levels. Thus, sound conditioning triggers an up-regulation of tyrosine hydroxylase both in the lateral efferent of cochlea and in the lateral superior olivary complex. These findings expand our understanding of the neurochemical balance and regulation between the lateral olivocochlear neurons and the lateral efferent terminals in the cochlea during sound stimulation.

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-

GABAergic neurons in the lateral superior olive of the hamster are distinguished by differential expression of gad isoforms during development

γ-Aminobutyric acid (GABA) is an inhibitory neurotransmitter that is synthesized by two isoforms of glutamic acid decarboxylase (GAD), GAD65 and GAD67. Using in situ hybridization and immunocytochemical techniques in hamsters, we investigated the postnatal development of GAD isoforms within the lateral superior olive (LSO) where GABAergic neurons form part of a descending efferent projection to the cochlea. In the neonatal hamster LSO, GAD67 immunoreactivity, GAD67 transcript labeling, and intense GABA immunostaining are at low levels. However, robust GAD65 mRNA expression is found throughout the LSO during the early postnatal period. The neonatal GABAergic expression patterns are in stark contrast to the adult where the LSO has robust GAD67 mRNA expression and weak GAD65 mRNA expression. Cells exhibiting intense GABA immunolabeling were also found in the same LSO locations as robust GAD67 mRNA expression and intense GAD67 immunoreactivity. Additionally, GAD67-positive cells in the LSO were retrogradely labeled from the cochlea confirming that these cells are a part of the lateral olivocochlear system. The late onset of GAD67 expression and intense GABA immunoreactivity in LSO neurons are consistent with the relatively late maturation of the lateral olivocochlear neurons inferred from previous studies. During development, these data lead us to conclude that the GABAergic portion of the lateral olivocochlear system is distinguished by preferential GAD67 expression, intense GABA immunoreactivity, and relatively late postnatal onset.

Dopaminergic innervation of the mouse inner ear: evidence for a separate cytochemical group of cochlear efferent fibers.

Immunostaining mouse cochleas for tyrosine hydroxylase (TH) and dopamine beta-hydroxylase suggests that there is a rich adrenergic innervation throughout the auditory nerve trunk and a small dopaminergic innervation of the sensory cell areas. Surgical cuts in the brainstem confirm these dopaminergic fibers as part of the olivocochlear efferent bundle. Within the sensory epithelium, TH-positive terminals are seen only in the inner hair cell area, where they intermingle with other olivocochlear terminals expressing cholinergic markers (vesicular acetylcholine transporter; VAT). Double immunostaining suggests little colocalization of TH and VAT; quantification of terminal volumes suggests that TH-positive fibers constitute only 10-20% of the efferent innervation of the inner hair cell area. Immunostaining of mouse brainstem revealed a small population of TH-positive cells in and around the lateral superior olive. Consistent with cochlear projections, double staining for the cholinergic marker acetylcholinesterase suggested that TH-positive somata are not cholinergic and vice versa. All observations are consistent with the view that a small dopaminergic subgroup of lateral olivocochlear neurons 1) projects to the inner hair cell area, 2) is distinct from the larger cholinergic group projecting there, and 3) may correspond to lateral olivocochlear "shell" neurons described by others (Warr et al. [1997] Hear. Res 108:89-111).

The Final Stage of Cholinergic Differentiation Occurs Below Inner Hair Cells During Development of the Rodent Cochlea

To gain further insights into the cholinergic differentiation of presynaptic efferent terminals in the inner ear, we investigated the expression of the high-affinity choline transporter (ChT1) in comparison to other presynaptic and cholinergic markers. In the adult mammalian cochlea, cholinergic axons from medial olivocochlear (OC) neurons form axosomatic synapses with outer hair cells (OHCs), whereas axons from lateral OC neurons form axodendritic synapses on afferent fibers below inner hair cells (IHCs). Mouse brain and cochlea homogenates reveal at least two ChT1 isoforms: a nonglycosylated approximately 73 kDa protein and a glycosylated approximately 45 kDa protein. In mouse brain, ChT1 is preferentially expressed by neurons in periolivary regions of the superior olive consistent with the location of medial OC neurons. In the adult mouse cochlea, ChT1-positive terminals are located almost exclusively below OHCs consistent with a medial OC innervation. Between postnatal day 2 (P2) and P4, ChT1-positive terminals are below IHCs and occur after the expression of growth-associated protein 43, synapsin, and the vesicular acetylcholine transporter. By P15, ChT1-positive terminals are mostly on OHCs. Accounting for differences in gestational age, the developmental expression of ChT1 in the rat cochlea is similar to the mouse. However, in older rats ChT1-positive terminals are below IHCs and OHCs. In both rat and mouse, our observations indicate that the onset of ChT1 expression occurs after efferent terminals are below IHCs and express other presynaptic and cholinergic markers. In the mouse, but not in the rat, ChT1 may preferentially identify medial OC neurons.

Disruption of lateral olivocochlear neurons via a dopaminergic neurotoxin depresses sound-evoked auditory nerve activity.

We applied the dopaminergic (DA) neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the guinea pig cochlear perilymph. Immunolabeling of lateral olivocochlear (LOC) neurons using antibodies against synaptophysin was reduced after the MPTP treatment. In contrast, labeling of the medial olivocochlear innervation remained intact. As after brainstem lesions of the lateral superior olive (LSO), the site of origin of the LOC neurons, the main effect of disrupting LOC innervation of the cochlea via MPTP was a depression of the amplitude of the compound action potential (CAP). CAP amplitude depression was similar to that produced by LSO lesions. Latency of the N1 component of the CAP, and distortion product otoacoustic emission amplitude and adaptation were unchanged by the MPTP treatment. This technique for selectively lesioning descending LOC efferents provides a new opportunity for examining LOC modulation of afferent activity and behavioral measures of perception.