3D model of frequency representation in the cochlear nucleus of the CBA/J mouse.

The relationship between structure and function is an invaluable context with which to explore biological mechanisms of normal and dysfunctional hearing. The systematic and topographic representation of frequency originates at the cochlea, and is retained throughout much of the central auditory system. The cochlear nucleus (CN), which initiates all ascending auditory pathways, represents an essential link for understanding frequency organization. A model of the CN that maps frequency representation in 3D would facilitate investigations of possible frequency specializations and pathologic changes that disturb frequency organization. Toward this goal, we reconstructed in 3D the trajectories of labeled auditory nerve (AN) fibers following multiunit recordings and dye injections in the anteroventral CN of the CBA/J mouse. We observed that each injection produced a continuous sheet of labeled AN fibers. Individual cases were normalized to a template using 3D alignment procedures that revealed a systematic and tonotopic arrangement of AN fibers in each subdivision with a clear indication of isofrequency laminae. The combined dataset was used to mathematically derive a 3D quantitative map of frequency organization throughout the entire volume of the CN. This model, available online (http://3D.ryugolab.com/), can serve as a tool for quantitatively testing hypotheses concerning frequency and location in the CN.

A monosynaptic pathway from dorsal cochlear nucleus to auditory cortex in rat.

Of the three major subdivisions of the auditory thalamus, the medial subdivision is the only one that receives a direct projection from the dorsal cochlear nucleus. Those cells in the medial auditory thalamus that receive the projection from the dorsal cochlear nucleus continue to the auditory cortex. A combination of anterograde and retrograde anatomical tracer injections made in the dorsal cochlear nucleus and the auditory cortex respectively, revealed terminal boutons which were directly apposed onto the dendrites and cell bodies of neurons in the medial auditory thalamus. The presence of a monosynaptic pathway, which transfers information from the first relay in the auditory system to the last, suggests that this pathway may rapidly convey very basic information to the auditory cortex.

Central auditory pathways mediating the rat middle ear muscle reflexes.

The middle ear muscle (MEM) reflexes function to protect the inner ear from intense acoustic stimuli and to reduce acoustic masking. Sound presented to the same side or to the opposite side activates the MEM reflex on both sides. The ascending limbs of these pathways must be the auditory nerve fibers originating in the cochlea and terminating in the cochlear nucleus, the first relay station for all ascending auditory information. The descending limbs project from the motoneurons in the brainstem to the MEMs on both sides, causing their contraction. Although the ascending and descending pathways are well described, the cochlear nucleus interneurons that mediate these reflex pathways have not been identified. In order to localize the MEM reflex interneurons, we developed a physiologically based reflex assay in the rat that can be used to determine the integrity of the reflex pathways after experimental manipulations. This assay monitored the change in tone levels and distortion product otoacoustic emissions within the ear canal in one ear during the presentation of a reflex-eliciting sound stimulus in the contralateral ear. Preliminary findings using surgical transection and focal lesioning of the auditory brainstem to interrupt the MEM reflexes suggest that MEM reflex interneurons are located in the ventral cochlear nucleus.

Medial olivocochlear reflex interneurons are located in the posteroventral cochlear nucleus: a kainic acid lesion study in guinea pigs.

The medial olivocochlear (MOC) reflex arc is probably a three-neuron pathway consisting of type I spiral ganglion neurons, reflex interneurons in the cochlear nucleus, and MOC neurons that project to the outer hair cells of the cochlea. We investigated the identity of MOC reflex interneurons in the cochlear nucleus by assaying their regional distribution using focal injections of kainic acid. Our reflex metric was the amount of change in the distortion product otoacoustic emission (at 2f(1)-f(2)) just after onset of the primary tones. This metric for MOC reflex strength has been shown to depend on an intact reflex pathway. Lesions involving the posteroventral cochlear nucleus (PVCN), but not the other subdivisions, produced long-term decreases in MOC reflex strength. The degree of cell loss within the dorsal part of the PVCN was a predictor of whether the lesion affected MOC reflex strength. We suggest that multipolar cells within the PVCN have the distribution and response characteristics appropriate to be the MOC reflex interneurons.

Acoustic stria: anatomy of physiologically characterized cells and their axonal projection patterns.

The mammalian cochlear nucleus (CN) has been a model structure to study the relationship between physiological and morphological cell classes. Several issues remain, in particular with regard to the projection patterns and physiology of neurons that exit the CN dorsally via the dorsal (DAS), intermediate (IAS), and commissural stria. We studied these neurons physiologically and anatomically using the intra-axonal labeling method. Multipolar cells with onset chopper (O(C)) responses innervated the ipsilateral ventral and dorsal CN before exiting the CN via the commissural stria. Upon reaching the midline they turned caudally to innervate the opposite CN. No collaterals were seen innervating any olivary complex nuclei. Octopus cells typically showed onset responses with little or no sustained activity. The main axon used the IAS and followed one of two routes occasionally giving off olivary complex collaterals on their way to the contralateral ventral nucleus of the lateral lemniscus (VNLL). Here they can have elaborate terminal arbors that surround VNLL cells. Fusiform and giant cells have overlapping but not identical physiology. Fusiform but not giant cells typically show pauser or buildup responses. Axons of both cells exit via the DAS and take the same course to reach the contralateral IC without giving off any collaterals en route.

Topographic anatomy of the cochlear nuclear region at the floor of the fourth ventricle in humans.

OBJECT: The development of appropriate methods to stimulate the dorsal and ventral cochlear nucleus by means of an auditory brainstem implant in patients with acquired bilateral anacusis requires a detailed topoanatomical knowledge both of the location and extension of the nuclear surface in the fourth ventricle and lateral recess and of its variability. The goal of this study was to provide that information. Anatomically, it is possible to use a midline surgical approach to the fourth ventricle rather than the translabyrinthine and suboccipital routes of access used hitherto. This is especially useful if severe scarring, which occurs as a result of tumor removal in the cerebellopontine angle, make the orientation and placement of an auditory brainstem implant via a lateral surgical approach difficult. There have been only a few studies, involving single cases and small series of patients, in which the focus was the exact extension of the cochlear nuclei, whose microsurgically relevant position in relation to the surface structures is not known in detail. METHODS: Landmarks that are important for the placement of an auditory brainstem implant through the fourth ventricle were examined and measured in a large series of 28 formalin-fixed human brainstems. In all cases, these examinations were supplemented by addition of a histological section series. For the first time values of unfixed fresh brainstem tissue were determined. Anatomical features are discussed with regard to their possible neurosurgical relevance, taking into account inter- and intraindividual variability. CONCLUSIONS: The midline approach would provide an opportunity to stimulate the whole area of the dorsal as well as the ventral cochlear nucleus with an auditory brainstem implant.

Morphology and axonal projection patterns of auditory neurons in the midbrain of the painted frog, Discoglossus pictus.

Acoustic signals are extensively used for guiding various behaviors in frogs such as vocalization and phonotaxis. While numerous studies have investigated the anatomy and physiology of the auditory system, our knowledge of intrinsic properties and connectivity of individual auditory neurons remains poor. Moreover, the neural basis of audiomotor integration still has to be elucidated. We determined basic response patterns, dendritic arborization and axonal projection patterns of auditory midbrain units with intracellular recording and staining techniques in an isolated brain preparation. The subnuclei of the torus semicircularis subserve different tasks. The principal nucleus, the main target of the ascending auditory input, has mostly intrinsic neurons, i.e., their dendrites and axons are restricted to the torus itself. In contrast, neurons of the magnocellular and the laminar nucleus project to various auditory and non-auditory processing centers. The projection targets include thalamus, tegmentum, periaqueductal gray, medulla oblongata, and in the case of laminar neurons--the spinal cord. Additionally, tegmental cells receive direct auditory input and project to various targets, including the spinal cord. Our data imply that both auditory and premotor functions are implemented in individual toral and tegmental neurons. Their axons constitute parallel descending pathways to several effector systems and might be part of the neural substrate for differential audiomotor integration.

The dorsal cochlear nucleus contributes to a high intensity component of the acoustic startle reflex in rats.

The dorsal cochlear nucleus (DCN) has been shown to project to a region of the nucleus reticularis pontis caudalis (PnC) critical for the evocation of startle in rats, suggesting a possible modulatory influence of the DCN on startle. This study examined the involvement of the DCN in the acoustic startle reflex and various other forms of behavioral plasticity seen with this response. Animals received bilateral electrolytic lesions of the DCN and were tested for acoustic startle responses, background noise facilitation, short-term habituation, prepulse inhibition and facilitation, and fear conditioning. Compared to sham lesioned rats, DCN lesioned rats showed a significant reduction in startle amplitude at the two highest startle-eliciting intensities (110 and 115 dB SPL) and normal responses on all other measures. Hence, the DCN appears to contribute to a high intensity component of the acoustic startle response in rats.

Inputs to a physiologically characterized region of the inferior colliculus of the young adult CBA mouse.

Presbycusis is a sensory perceptual disorder involving loss of high-pitch hearing and reduced ability to process biologically relevant acoustic signals in noisy environments. The present investigation is part of an ongoing series of studies aimed at discerning the neural bases of presbycusis. The purpose of the present experiment was to delineate the inputs to a functionally characterized region of the dorsomedial inferior colliculus (IC, auditory midbrain) in young, adult CBA mice. Focal, iontophoretic injections of horseradish peroxidase were made in the 18-24 kHz region of dorsomedial IC of the CBA strain following physiological mapping experiments. Serial sections were reacted with diaminobenzidine or tetramethylbenzidine, counterstained and examined for retrogradely labeled cell bodies. Input projections were observed contralaterally from: all three divisions of cochlear nucleus; intermediate and dorsal nuclei of the lateral lemniscus (LL); and the central nucleus, external nucleus and dorsal cortex of the IC. Input projections were observed ipsilaterally from: the medial and lateral superior olivary nuclei; the superior paraolivary nucleus; the dorsolateral and anterolateral periolivary nuclei; the dorsal and ventral divisions of the ventral nucleus of LL; the dorsal and intermediate nuclei of LL; the central nucleus, external nucleus and dorsal cortex of the IC outside the injection site; and small projections from central gray and the medial geniculate body. These findings in young, adult mice with normal hearing can now serve as a baseline for similar experiments being conducted in mice of older ages and with varying degrees of hearing loss to discover neural changes that may cause age-related hearing disorders.