Descending projections from the inferior colliculus to medial olivocochlear efferents: Mice with normal hearing, early onset hearing loss, and congenital deafness.

Auditory efferent neurons reside in the brain and innervate the sensory hair cells of the cochlea to modulate incoming acoustic signals. Two groups of efferents have been described in mouse and this report will focus on the medial olivocochlear (MOC) system. Electrophysiological data suggest the MOC efferents function in selective listening by differentially attenuating auditory nerve fiber activity in quiet and noisy conditions. Because speech understanding in noise is impaired in age-related hearing loss, we asked whether pathologic changes in input to MOC neurons from higher centers could be involved. The present study investigated the anatomical nature of descending projections from the inferior colliculus (IC) to MOCs in 3-month old mice with normal hearing, and in 6-month old mice with normal hearing (CBA/CaH), early onset progressive hearing loss (DBA/2), and congenital deafness (homozygous Shaker-2). Anterograde tracers were injected into the IC and retrograde tracers into the cochlea. Electron microscopic analysis of double-labelled tissue confirmed direct synaptic contact from the IC onto MOCs in all cohorts. These labelled terminals are indicative of excitatory neurotransmission because they contain round synaptic vesicles, exhibit asymmetric membrane specializations, and are co-labelled with antibodies against VGlut2, a glutamate transporter. 3D reconstructions of the terminal fields indicate that in normal hearing mice, descending projections from the IC are arranged tonotopically with low frequencies projecting laterally and progressively higher frequencies projecting more medially. Along the mediolateral axis, the projections of DBA/2 mice with acquired high frequency hearing loss were shifted medially towards expected higher frequency projecting regions. Shaker-2 mice with congenital deafness had a much broader spatial projection, revealing abnormalities in the topography of connections. These data suggest that loss in precision of IC directed MOC activation could contribute to impaired signal detection in noise.

The course and distribution of medial efferent fibers in the cochlea of the mustached bat.

The course and distribution of medial olivocochlear (MOC) nerve fibers were studied in the cochlea of the mustached bat. This animal is of interest because of the very sharp tuning of the ear and fine frequency resolution in small frequency bands near 60 and 90 kHz. The MOC fibers arise from about 400 cells in the dorsomedial periolivary (DMPO) nucleus and they are distributed to approximately 4500 outer hair cells (OHCs), resulting in an average OHC unit size of 11.25. Individual fibers appear to have a small number of branches and each branch entering the tunnel of Corti terminates on a patch of OHCs. The patch size is typically 1-3 OHCs with the smallest average patch sizes in the regions tuned to 60 and 90 kHz. The majority of the MOC terminals are derived from the contralateral DMPO. Contralateral vs. ipsilateral projecting fibers are not preferentially distributed within any of the three rows of OHCs or within specific regions throughout most of the cochlea. It can be concluded that the main differences between the mustached bat's MOC system and that of most other mammals are: (1) origin from a single nucleus; (2) relatively small sizes of the patches; (3) a single terminal on each OHC; (4) a gradient in the size of the terminals but not in the number of terminals from row to row or from base to apex.

Effects of a dopaminergic agonist in the guinea pig cochlea.

This study investigates the role of dopamine, a putative lateral efferent neurotransmitter/modulator, in cochlear physiology and physiopathology. Cochlear potentials were recorded in guinea pigs after intracochlear perfusion of increasing doses (0.1-1 mM) of piribedil, an agonist of the D2/D3 receptors. A dose-dependent reduction in the amplitude of auditory nerve compound action potential (CAP) was observed, predominantly at high-intensity tone-burst stimulations, and without significant effect on CAP threshold. There was no variation of cochlear microphonic and summating potential. When 1 mM piribedil was perfused into the cochlea during continuous 130 dB SPL pure tone exposure (6 kHz, 15 min), CAP threshold shifts were significantly less than in control animals with artificial perilymph-perfused cochleas. No dendritic damage was observed, although there was evident hair cell damage. Similarly, radial dendrites were clearly protected against ischemia-induced damage when 1 mM piribedil was applied prior to a 10-min ischemia. These results suggest that dopamine modulates the activity of radial afferent fibers via D2/D3 receptors. The protective effect of piribedil during acoustic trauma or ischemia suggests that this modulation corresponds to a prevention of excitotoxicity due to dysfunction of inner hair cell neurotransmission.

GABAergic terminals in nucleus magnocellularis and laminaris originate from the superior olivary nucleus.

The auditory brainstem nuclei, angularis (NA), magnocellularis (NM), and laminaris (NL) of the chicken, Gallus, contain terminals that stain for antibodies against the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). Some of these terminals originate from cells surrounding nucleus magnocellularis. Results from this study indicate that the majority of the GABAergic terminals found in NA, NM and NL originate from the superior olivary nucleus (SON). Injections of cholera toxin and horseradish peroxidase show that superior olivary nucleus (SON) neurons, which respond to pure tones, project bilaterally to NA, NM, and NL. NA and NL are reciprocally connected with the SON. More NA cells project to the SON than NL cells. While SON neurons project to NM, NM neurons do not project axons back to the SON. The configuration of SON terminals in NA, NM and NL matches the pattern of GABA-immunoreactive puncta seen in these three nuclei: they surround individual NM cells, congregate in the dendritic neuropil of NL, and blanket the NA. The data indicate that NA, NM and NL may be affected by two different inhibitory cell types: local interneurons and SON neurons. Patterns of connectivity described in this report suggest that the activity of NA cells could influence NM and NL cell physiology. Specifically, increases in NA cell activity could augment the effects of GABAergic SON neurons on NM and NL. Hence, binaural perception in the chicken may be more dependent upon changes in intensity cues than previously believed.

Structural and functional properties distinguish two types of multipolar cells in the ventral cochlear nucleus.

We distinguish two types of large multipolar cells designated sustained (CS) and onset (OC) choppers in the anterior posteroventral cochlear nucleus (A-PVCN)/nerve root region on the basis of certain anatomical and physiological features. CS axons head into the trapezoid body, while OC axons use the intermediate acoustic stria of Held. At the electron microscopic (EM) level, collateral terminals of OC axons contain pleomorphic vesicles; CS terminals contain small round vesicles. CS dendritic trees tend to be distributed in a stellate fashion while OC dendritic trees tend to be elongated. At the EM level the sustained chopper somata are sparsely innervated while the proximal dendritic tree receives considerably more input. The OC somata are highly innervated and this heavy innervation continues out onto the proximal dendrites. Distally the dendritic innervation falls off considerably for both categories. Physiologically, members of the OC population have wider dynamic ranges at the characteristic frequency (CF), wider response areas that are typically not flanked by inhibitory sidebands, and responses to short tones that do not show the same form of regularity expressed by sustained choppers. Intracellularly the sustained choppers exhibit sustained depolarization to short tones for the duration of the stimulus with resultant regular spiking at a rate that is stimulus level dependent. The response to swept tone shows this same level-dependent regularity. In response to tones, the OC cells also show a sustained depolarization whose amplitude is stimulus-level dependent but whose range is much greater and whose onset is initiated more abruptly. Although the onset component of the OC spike output is reliably initiated by these levels of depolarization, regular firing to the sustained depolarization is not initiated at levels of depolarization that would surely generate regular firing in sustained choppers. This regularity is also absent in the swept tone response despite marked levels of excitation.