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Differential calbindin-like immunoreactivity in the brain stem auditory system of the chinchilla.

Calbindin is a 28 kD calcium-binding protein found in neural tissue. Although its functional role in neurons is unknown, it has been proposed that calbindin is involved in intracellular buffering and could therefore influence temporal precision of neuronal firing. In the barn owl, calbindin-like immunoreactivity was found to be selectively present in brain stem auditory pathways used to process interaural time differences, but was absent from the interaural intensity pathway. The present study demonstrates calbindin immunoreactivity in the auditory brain stem of the chinchilla, a rodent with exceptionally good low-frequency hearing. In the superior olivary complex and periolivary areas, immunoreactivity was divided between neuropil labeling in the lateral and medial superior olives and dorsomedial periolivary nucleus, and labeling of the somata of the medial and ventral nuclei of the trapezoid body and anterolateral periolivary nucleus. Strong immunoreactivity was observed in the ventral and dorsal divisions of the ventral nucleus of lateral lemniscus somata and the ventral division's columnarly organized fiber plexus. The dorsal nucleus of the lateral lemniscus was void of immunoreactivity. Virtually all principal neurons of the sagulum showed darkly labeled somata surrounded by a densely labeled fiber plexus. Immunoreactivity in the inferior colliculus was primarily limited to the paracentral nuclei, with only an occasional labeled cell in the central nucleus. In conclusion, although selective labeling of calbindin in the mammalian auditory brain stem is impressive, no distinctive labeling of a functionally defined timing pathway was apparent as reported previously in the barn owl or electric fish.

Animals↗

Decreased temporal precision of auditory signaling in Kcna1-null mice: an electrophysiological study in vivo.

The voltage-gated potassium (Kv) channel subunit Kv1.1, encoded by the Kcna1 gene, is expressed strongly in the ventral cochlear nucleus (VCN) and the medial nucleus of the trapezoid body (MNTB) of the auditory pathway. To examine the contribution of the Kv1.1 subunit to the processing of auditory information, in vivo single-unit recordings were made from VCN neurons (bushy cells), axonal endings of bushy cells at MNTB cells (calyces of Held), and MNTB neurons of Kcna1-null (-/-) mice and littermate control (+/+) mice. Thresholds and spontaneous firing rates of VCN and MNTB neurons were not different between genotypes. At higher sound intensities, however, evoked firing rates of VCN and MNTB neurons were significantly lower in -/- mice than +/+ mice. The SD of the first-spike latency (jitter) was increased in VCN neurons, calyces, and MNTB neurons of -/- mice compared with +/+ controls. Comparison along the ascending pathway suggests that the increased jitter found in -/- MNTB responses arises mostly in the axons of VCN bushy cells and/or their calyceal terminals rather than in the MNTB neurons themselves. At high rates of sinusoidal amplitude modulations, -/- MNTB neurons maintained high vector strength values but discharged on significantly fewer cycles of the amplitude-modulated stimulus than +/+ MNTB neurons. These results indicate that in Kcna1-null mice the absence of the Kv1.1 subunit results in a loss of temporal fidelity (increased jitter) and the failure to follow high-frequency amplitude-modulated sound stimulation in vivo.

Acoustic Stimulation↗

The late Nd reflects a memory trace containing amodal spatial information.

The early Nd reflects the analysis of simple features of selectively attended auditory stimuli, but the precise nature of the more complex processing reflected by the late Nd is unclear. The late but not the early Nd is sensitive to interference from a concurrently presented visual spatial attention switching task. This experiment investigated whether the late Nd is also sensitive to deeper visual attention switching. Twenty-one subjects performed a dichotic listening task concurrently with either visual spatial or visual letter matching attention switching tasks. Late Nd amplitude was reduced by the spatial but not the letter matching task, indicating insensitivity to deeper attention switching. P300 amplitude was reduced by both tasks. Reductions in N100 and P200 were uncorrelated. We propose that, in part, the late Nd reflects an amodal memory trace containing spatial information, possibly involving a "where" rather than a "what" auditory pathway.

Adolescent↗

Comparison of midbrain and thalamic space-specific neurons in barn owls.

Spatial receptive fields of neurons in the auditory pathway of the barn owl result from the sensitivity to combinations of interaural time (ITD) and level differences across stimulus frequency. Both the forebrain and tectum of the owl contain such neurons. The neural pathways, which lead to the forebrain and tectal representations of auditory space, separate before the midbrain map of auditory space is synthesized. The first nuclei that belong exclusively to either the forebrain or the tectal pathways are the nucleus ovoidalis (Ov) and the external nucleus of the inferior colliculus (ICx), respectively. Both receive projections from the lateral shell subdivision of the inferior colliculus but are not interconnected. Previous studies indicate that the owl's tectal representation of auditory space is different from those found in the owl's forebrain and the mammalian brain. We addressed the question of whether the computation of spatial cues in both pathways is the same by comparing the ITD tuning of Ov and ICx neurons. Unlike in ICx, the relationship between frequency and ITD tuning had not been studied in single Ov units. In contrast to the conspicuous frequency independent ITD tuning of space-specific neurons of ICx, ITD selectivity varied with frequency in Ov. We also observed that the spatially tuned neurons of Ov respond to lower frequencies and are more broadly tuned to ITD than in ICx. Thus there are differences in the integration of frequency and ITD in the two sound-localization pathways. Thalamic neurons integrate spatial information not only within a broader frequency band but also across ITD channels.

Acoustic Stimulation↗

Contribution of AMPA and NMDA receptors to excitatory responses in the inferior colliculus.

Brain slice studies of neurons in the central nucleus of the inferior colliculus (ICC) indicate that excitatory responses evoked by electrical stimulation of the lateral lemniscus consist of two components, an early, rapid response mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and a later, a slower one mediated by N-methyl-D-aspartate (NMDA) receptors. The early response can be selectively blocked by AMPA receptor antagonists (1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium [NBQX]; or 6-cyano-7-nitroquinoxaline-2,3-dione) [CNQX], and the later one by NMDA receptor antagonists ((+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid [CPP]; or (+/-)-2-amino-5-phosphonovaleric acid) [APV]. Both AMPA and NMDA receptor-mediated responses can be elicited at resting potential, although the NMDA response is voltage dependent and makes a greater contribution when the cell membrane is depolarized. In vivo studies indicate that both AMPA and NMDA receptors contribute to sound-evoked responses. Both AMPA and NMDA receptor antagonists reduce the firing rate of single neurons in the ICC to contralaterally presented tones. Both classes of antagonist lower evoked activity over a wide range of sound intensities from threshold to maximum sound pressure levels. Thus, both NMDA and AMPA receptors contribute to responses over the full dynamic range of auditory sensitivity. The AMPA receptor antagonist, NBQX, is more effective than the NMDA receptor antagonist, CPP, in blocking responses of onset cells. Furthermore, NBQX and CPP have preferential effects in blocking the early or late responses of neurons that exhibited sustain activity to a 100 ms tone. Excitatory responses to sinusoidally amplitude-modulated stimuli are also reduced by application of either AMPA or NMDA antagonists. However, the synchrony of firing of action potentials to the modulation period (vector strength) is largely unaffected. The data suggest that the synchrony of firing of neurons in the inferior colliculus is determined primarily by the pattern of activity at lower levels of the auditory pathway and/or the local intrinsic properties of the cells.

Acoustic Stimulation↗

Three frequency component waveforms of auditory evoked brainstem response in spinocerebellar degeneration.

Under adequate stimulus intensities, the power spectra of normal auditory evoked brainstem responses (ABRs) are composed of three major components: 0-350 Hz, 350-700 Hz and 700-1200 Hz. By means of a digital filter using fast Fourier transform, three ABR waveforms consisting of each frequency component of the power spectrum were obtained. The significance of these three component waveforms in the analysis of ABR abnormality was estimated in 30 patients with spinocerebellar degeneration (SCD). In conventional wave latency analysis, 9 out of 30 patients (30%) had abnormal ABRs, the main abnormality being prolonged interpeak latencies of waves I-III, I-V and the disappearance of wave V. On the other hand, component waveforms were abnormal in 82.5% of the cases. These results suggest that analysis of ABRs by the use of component waveforms is useful for detecting abnormality in the brainstem auditory pathway in SCD patients.

Audiometry, Evoked Response↗

Asymmetrical enhancement of middle-latency auditory evoked fields with aging.

We studied the effects of aging on middle-latency auditory evoked fields (P50m), and analyzed their interhemispheric differences. Magnetic responses following tone-burst stimuli to the right ear were measured in groups of 11 younger and 15 elderly subjects. The elderly subjects showed marked asymmetry in the P50m amplitudes. In the elderly group, the mean amplitude of the contralateral P50m was significantly larger (P<0.0005) than that of the ipsilateral P50m, while no asymmetry was shown in the younger group. The amplitude enlargement in the contralateral P50m showed significant correlation with age (R=0.60, P<0.005), while the ipsilateral P50m showed no correlation with age. These results suggest that the contralateral and ipsilateral auditory pathways are affected differently by ageing.

Aged↗

Eph proteins and the assembly of auditory circuits.

Many kinds of information are carried in the acoustic signal that reaches auditory receptor cells in the cochlea. The analysis of this information is possible in large part because of the neuronal architecture of the auditory system. The mechanisms that establish the precise circuitry that underlies auditory processing have not yet been identified. The Eph receptor tyrosine kinases and their ligands are proteins that regulate axon guidance and have been shown to contribute to the establishment of topographic projections in several areas of the nervous system. Several studies have begun to investigate whether these proteins are involved in the formation of auditory system connections. Studies of gene expression show that Eph proteins are extensively expressed in structures of the inner ear as well as in neurons in the peripheral and central components of the auditory system. Functional studies have demonstrated that Eph signaling influences the assembly of auditory pathways. These studies suggest that Eph protein signaling has a significant role in the formation of auditory circuitry.

Animals↗

The AMPA receptors of auditory neurons.

The ionotropic glutamate receptor (GluR) subtype known as the AMPA receptor, which mediates rapid excitatory synaptic transmission in many regions of the nervous system, is composed of four different protein subunits, termed GluRs 1-4. The functional properties of each AMPA receptor are determined by the relative levels of GluRs 1-4 and by post-transcriptional modifications of these proteins through mRNA editing and alternative exon splicing. The present paper reviews the published evidence for (1) localization of mRNAs and immunoreactivity for GluRs 1-4 in the cochlea and subcortical central nervous system auditory pathways of mammals and birds, and (2) involvement of AMPA receptors in synaptic transmission in the auditory system. Recent biochemical and electrophysiological evidence concerning the specialized properties of AMPA receptors on brainstem auditory neurons is also reviewed, along with data concerning how these properties emerge during normal development.

Animals↗

Intracellular chloride and calcium transients evoked by gamma-aminobutyric acid and glycine in neurons of the rat inferior colliculus.

Microfluorometric recordings showed that the inhibitory neurotransmitters gamma-aminobutyric acid (GABA) and glycine activated transient increases in the intracellular Cl- concentration in neurons of the inferior colliculus (IC) from acutely isolated slices of the rat auditory midbrain. Current recordings in gramicidin-perforated patch mode disclosed that GABA and glycine mainly evoked inward or biphasic currents. These currents were dependent on HCO3- and characterized by a continuous shift of their reversal potential (E(GABA/gly)) in the positive direction. In HCO3- -buffered saline, GABA and glycine could also evoke an increase in the intracellular Ca2+ concentration. Ca2+ transients occurred only with large depolarizations and were blocked by Cd2+, suggesting an activation of voltage-gated Ca2+ channels. However, in the absence of HCO3-, only a small rise, if any, in the intracellular Ca2+ concentration could be evoked by GABA or glycine. We suggest that the activation of GABAA or glycine receptors results in an acute accumulation of Cl- that is enhanced by the depolarization owing to HCO3- efflux, thus shifting E(GABA/gly) to more positive values. A subsequent activation of these receptors would result in a strenghtened depolarization and an enlarged Ca2+ influx that might play a role in the stabilization of inhibitory synapses in the auditory pathway.

Animals↗

Ascending efferent projections of the superior olivary complex.

The superior olivary complex conveys information about binaural time and intensity to higher centers in the auditory pathway. This information is sent primarily to the subdivisions of the inferior colliculus and to the nuclei of the lateral lemniscus. Olivary projections are the predominant afferents to the central nucleus of the inferior colliculus. Electron microscopic observations of axonal endings in the central nucleus suggest that the ipsilateral medial superior olive and contralateral lateral superior olive make excitatory synapses. In contrast, the axons from the ipsilateral lateral superior olive to the central nucleus contain glycine and have a morphology consistent with inhibitory synapses. Little is known about the transmitter types used by olivary projections to the nuclei of the lateral lemniscus, but they are presumed to be similar to the collicular projections. Olivary ascending efferents are tonotopically organized and terminate in laminae in the inferior colliculus. They combine with other laminar afferents and postsynaptic neurons to create fibro-dendritic laminae in the colliculus. The key to the functional organization of the olivary efferents is the possible segregation of excitatory olivary efferents from each other in "synaptic domains" located on the laminae. This segregation may be the major determinant of response properties in the colliculus. Olivary efferents may converge with other non-olivary afferents on the same postsynaptic neurons in the colliculus. Inhibitory efferents from the lateral superior olive are essential in shaping the response properties of neurons in the colliculus. Olivary efferents to the nuclei of the lateral lemniscus are also key components of ascending pathways that inhibit neurons in the midbrain.

Animals↗

Evidence for the delayed expression of a brainstem abnormality in albino ferrets.

Previous reports have suggested that neurons of the medial superior olivary nucleus in albino cats and rabbits are smaller than those in normally pigmented strains. In this investigation, the mean cross-sectional areas of neuronal perikarya in the medial superior olivary nucleus of pigmented and albino ferrets were compared at juvenile (14 weeks) and adult (greater than six months) ages. The mean cross-sectional area of the perikarya in adult albino ferrets was found to be 45% smaller than that of adult pigmented ferrets, confirming observations in cat and rabbit. The same comparison in juvenile ferrets, however, showed no significant differences. These results suggest that the mechanisms producing the abnormality of the auditory pathways differ from those responsible for the production of abnormal retinofugal pathways in albinos.

Albinism↗

Development of tonotopic representation in the Mongolian gerbil: a 2-deoxyglucose study.

The spatial representation of frequency in the central auditory system of the neonatal gerbil was mapped with the 2-deoxyglucose (2-DG) autoradiographic technique. At 14 days after birth (DAB), pure tone stimulation produced recognizable patterns of 2-DG uptake. However, at this age, tone-induced areas of increased 2-DG uptake occurred at locations which in the adult respond to higher frequencies. The degree of shift in tonotopic representation was approximately two octaves. The normal adult tonotopic organization of auditory nuclei was achieved by 18 DAB, consistent with the rapid development of auditory function in the gerbil. The results suggest that the spatial distribution of frequency in the cochlea of neonatal animals is different from that in adults. Stimulus-evoked 2-DG uptake occurred first in brainstem auditory nuclei, and was observed in midbrain and forebrain auditory structures only at later ages. This is consistent with a sequential development of function in the central auditory pathway.

Acoustic Stimulation↗

Auditory-vocal cholinergic pathway in zebra finch brain.

The two main song control nuclei in the zebra finch forebrain, the higher vocal center (HVC) and the robust nucleus of the archistriatum (RA), receive cholinergic innervation from the ventral paleostriatum (VP) of the basal forebrain which may play a key role in song learning. By injecting two kinds of neuroanatomical tracers, we found that a topographically segregated pathway from nucleus ovoidalis (Ov) and nucleus dorsomedialis posterior thalami (DMP) to VP and further to RA and HVC. Ov is known as a major relay in the main ascending auditory pathway. The results suggest that cholinergic neurons in the VP which are responsible for song learning are regulated by auditory information from the Ov.

Acetylcholine↗

Acoustic noise and functional magnetic resonance imaging: current strategies and future prospects.

Functional magnetic resonance imaging (fMRI) has become the method of choice for studying the neural correlates of cognitive tasks. Nevertheless, the scanner produces acoustic noise during the image acquisition process, which is a problem in the study of auditory pathway and language generally. The scanner acoustic noise not only produces activation in brain regions involved in auditory processing, but also interferes with the stimulus presentation. Several strategies can be used to address this problem, including modifications of hardware and software. Although reduction of the source of the acoustic noise would be ideal, substantial hardware modifications to the current base of installed MRI systems would be required. Therefore, the most common strategy employed to minimize the problem involves software modifications. In this work we consider three main types of acquisitions: compressed, partially silent, and silent. For each implementation, paradigms using block and event-related designs are assessed. We also provide new data, using a silent event-related (SER) design, which demonstrate higher blood oxygen level-dependent (BOLD) response to a simple auditory cue when compared to a conventional image acquisition.

Auditory Pathways↗

Activation of the auditory cortex by cochlear stimulation in a deaf patient.

We have recorded cerebral electric and magnetic responses to electric stimulation of the auditory nerve in a deaf patient with multichannel cochlear prosthesis. The electric response peaked with a vertex-negative deflection at 65 ms. Clear magnetic responses, coinciding with the vertex potential, were obtained only over the hemisphere ipsilateral to the stimulation; the field pattern indicated activation of the auditory cortex within the Sylvian fissure. The results suggest modification of the central auditory pathways in this patient deaf from early childhood.

Auditory Cortex↗

Connectionist networks in auditory system modeling.

Understanding how complex sounds, such as speech, are processed and eventually perceived in the brain is essential for building more effective speech processors. The echolocating bat provides an animal model for complex-sound processing of identified stimulus features at higher levels of the auditory pathway. In this paper, we present the use of connectionist models for modeling cortical neurons that play a key role in our auditory system model of a species of FM bat, Myotis lucifugus. The influence of network related parameters on modeling accuracy is presented, and the response of these models is explained in a behavioral context.

Acoustic Stimulation↗

A longitudinal study of brainstem auditory evoked potentials of preterm infants.

Brainstem auditory evoked potentials (BAEPs) of nine 'healthy' preterm infants were recorded at weekly intervals between 32 and 36 weeks conceptional age to study the relationship between stimulus intensity and central transmission time through the subcortical auditory pathway (i.e. the interval latency between peak I and peak V) as a function of conceptional age. Stimulus intensities of 70, 80 and 90 dB nHTL were used. Changes in click intensity produced changes in the absolute latency of all BAEP peaks, but the interval latency I to V remained constant. The absolute latencies and interval latencies reflected maturity, but varied widely between these preterm infants. The peak V latency and the I to V interval latency decreased with increasing conceptional age. Exponential regression analysis suggested that, above 70 dB nHTL, the time-constant of the calculated exponential function most likely represents maturation and function of the central subcortical pathway, and may give an indication of the infants' development.

Auditory Pathways↗