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Implications of neurotrophin supported auditory neuron survival for maintenance of the tonotopic organization of the central auditory pathway.

Recent experiments have demonstrated the effectiveness of members of the neurotrophin family of growth factors in supporting the survival of primary auditory neurons following ototoxic trauma. In this report, we examined the implications of these results in light of current knowledge about activity dependent central nervous system reorganization. We suggest that the use of trophic factors in conjunction with patterned stimulation of afferent nerve fibers could preserve the majority of the tonotopic arrangement of the central pathway. We propose experiments to test the effects of NT-3 induced neuron survival on the organization of primary auditory cortex.

Animals↗

Regeneration of the auditory pathway in adult rats by transplants of fetal brain tissue.

The ventral cochlear tract in the brain stem to pons was transected on one side in two groups of adult rats. In one group simple transection was performed, while in the other group tissue from embryos (E14-E16) was used to cover the lesion site. While rats receiving simple transection without transplantation showed no evidence of regeneration, in 30% of the rats receiving transplants of embryonic tissue the axons regrew beyond the transected site and regenerated into the denervated side and terminated at the normal targets. The present findings contradict the widely held view that the adult mammalian central auditory system cannot be restored following damage.

Animals↗

Neuronal organization of the rat inferior colliculus participating in four major auditory pathways.

The central nucleus of the inferior colliculus (CNIC) contains different types of neurons and is a source of ascending projection to the medial geniculate body (MGB), commissural projection to the contralateral IC, direct descending projection to the cochlea nucleus (CN) and indirect projection to the CN via the superior olivary complex (SOC). Using a retrograde tracing technique, we examined what kind of neurons and what percentage of neurons of each type recognized in the CNIC participated in the above-mentioned four projection pathways. We also examined whether the individual CNIC neurons send the collateral to the MGB, the contralateral IC, the CN and the SOC. In the present study, we demonstrated that the neurons participating in the four projections could be morphologically classified into two types of neurons with soma size variation. The percentages of neurons of each type differed among the four projection pathways. Using a double-labeling technique, we found very few double-labeled neurons, indicating the collateral projections to the ipsilateral MGB and the contralateral IC. There were no double-labeled neurons in the collateral projections between the other combinations of targets. Therefore, we conclude that the ascending projection, the commissural projection and the descending projection to these targets arise from separate populations of neurons.

Animals↗

Non-surgical recording of auditory pathway function in cats.

The techniques are described for serial, non-surgical recording of the cochlear microphonic (CM), the electrocochleogram (ECoG) and the averaged electroencephalic response (AER) in cats. The early post-natal period has been systematically studied in a breeding strain of hereditarily deaf white cats, and illustrative examples are presented from animals with histologically normal chochleae, and also from ears with confirmed chochleosaccular degeneration. Transitory potentials have been recorded with the CM and ECoG procedures from some of the latter.

Age Factors↗

[Tumor-induced function disorders of the acoustic nerve and the lower portions of the auditory pathway].

The manyfold features of acoustic neuromas, respectively tumors of the cerebello pontine angle, are tried to explain by pathophysiologic phenomena of the neural conduction. They are the pathologic fatigue of hearing, the disturbed excitability of the acustico facial stapedial reflex, the impaired velocity of nerve conduction, a poor synchronization of conduction as well as the excessively reduced monosyllabic and dichotic discrimination. With respect to the original tissue, localization, size as well as regional spread and growth pressure there result different constellations of symptoms, eventually only marked discretely. However, all 35 tumors of a defined observation period as well could be diagnosed solely by functional hearing tests.

Adult↗

Anatomical identification of an auditory pathway from a nucleus of the lateral lemniscal system to the frontal telencephalon (nucleus basalis) of the pigeon.

Anterograde and retrograde tracing experiments employing WGA-HRP were used to identify an auditory projection area within the frontal telencephalon of the pigeon. The projection originates in a nucleus of the lateral lemniscus, travels with the quintofrontal tract and terminates within nucleus basalis. The location of the projection area and the absence of a thalamic relay in its pathway are consistent with previous reports of short-latency auditory potentials evoked in the vicinity of the nucleus basalis in several avian species.

Animals↗

Regulation of the voltage-gated potassium channel KCNQ4 in the auditory pathway.

The potassium channel KCNQ4, expressed in the mammalian cochlea, has been associated tentatively with an outer hair cell (OHC) potassium current, I(K,n), a current distinguished by an activation curve shifted to exceptionally negative potentials. Using CHO cells as a mammalian expression system, we have examined the properties of KCNQ4 channels under different phosphorylation conditions. The expressed current showed the typical KCNQ4 voltage-dependence, with a voltage for half-maximal activation (V(1/2)) of -25 mV, and was blocked almost completely by 200 microM linopirdine. Application of 8-bromo-cAMP or the catalytic sub-unit of PKA shifted V(1/2) by approximately -10 and -20 mV, respectively. Co-expression of KCNQ4 and prestin, the OHC motor protein, altered the voltage activation by a further -15 mV. Currents recorded with less than 1 nM Ca(2+) in the pipette ran down slowly (12% over 5 min). Buffering the pipette Ca(2+) to 100 nM increased the run-down rate sevenfold. Exogenous PKA in the pipette prevented the effect of elevated [Ca(2+)](i) on run-down. Inhibition of the calcium binding proteins calmodulin or calcineurin by W-7 or cyclosporin A, respectively, also prevented the calcium-dependent rapid run-down. We suggest that KCNQ4 phosphorylation via PKA and coupling to a complex that may include prestin can lead to the negative activation and the negative resting potential found in adult OHCs.

Animals↗

The binaural auditory pathway: excitatory amino acid receptors mediate dual timecourse excitatory postsynaptic currents in the rat medial nucleus of the trapezoid body.

We show here that synaptic transmission to the medial nucleus of the trapezoid body (MNTB) is mediated principally by excitatory amino acid receptors and has two components. A fast excitatory postsynaptic current (EPSC) is mediated by non-NMDA receptors and a slow EPSC is mediated by NMDA receptors. Each neuron receives a large synaptic input (calyx of Held) which produces an EPSC with a mean peak conductance of 37 nS. The somatic location of this synapse gives good resolution of the EPSC timecourse with the fast EPSC decaying with a time constant of 1.1 ms (at 25 degrees C). The slow EPSC exhibits a double exponential decay with time constants of 41 ms and 106 ms and is voltage dependent in the presence of extracellular magnesium. Other smaller EPSCS mediated by NMDA and non-NMDA receptors, and a strychnine-sensitive synaptic current, are also present. Although the intrinsic membrane properties of MNTB neurons (Forsythe & Barnes-Davies (Proc. R. Soc. Lond. B 251, 143 (1993)), preceding paper) promote high-fidelity transmission, we show that voltage-dependent modulation of synaptic transmission can occur. Given the specialization of the calyx of Held, it seems that the NMDA-receptor ion channel complex is not primarily serving to potentiate a subthreshold input, but may be involved in the development and maintenance of this exuberant somatic synapse.

Animals↗

Parallel auditory pathways: projection patterns of the different neuronal populations in the dorsal and ventral cochlear nuclei.

The cochlear nuclear complex gives rise to widespread projections to nuclei throughout the brainstem. The projections arise from separate, well-defined populations of cells. None of the cell populations in the cochlear nucleus projects to all brainstem targets, and none of the targets receives inputs from all cell types. The projections of nine distinguishable cell types in the cochlear nucleus-seven in the ventral cochlear nucleus and two in the dorsal cochlear nucleus-are described in this review. Globular bushy cells and two types of spherical bushy cells project to nuclei in the superior olivary complex that play roles in sound localization based on binaural cues. Octopus cells convey precisely timed information to nuclei in the superior olivary complex and lateral lemniscus that, in turn, send inhibitory input to the inferior colliculus. Cochlear root neurons send widespread projections to areas of the reticular formation involved in startle reflexes and autonomic functions. Type I multipolar cells may encode complex features of natural stimuli and send excitatory projections directly to the inferior colliculus. Type II multipolar cells send inhibitory projections to the contralateral cochlear nuclei. Fusiform cells in the dorsal cochlear nucleus appear to be important for the localization of sounds based on spectral cues and send direct excitatory projections to the inferior colliculus. Giant cells in the dorsal cochlear nucleus also project directly to the inferior colliculus; some of them may convey inhibitory inputs to the contralateral cochlear nucleus as well.

Animals↗

Changes of 2-deoxyglucose uptake in the rat auditory pathway after bilateral ablation of the cochlea.

It has been reported that the area of decreased glucose metabolism in the FDG-PET of prelingually deaf children correlates significantly with speech performance after cochlear implantation. In this study, we undertook to confirm changes of glucose metabolism in the cerebral cortex using an animal model with age-matching groups to completely exclude the influence of age differences between the deaf and normal-hearing groups. The cochlea was ablated bilaterally at a postnatal 10-14 days in the deaf groups; 3-4 deaf and normal rats were included at each time point at 1, 2, 4 and 8 weeks and 7 months after ablation. After injecting 2-deoxyglucose intraperitoneally, digitalized autoradiographic images were obtained, and analyzed by using two different methods; 3-dimensional voxel-wise statistical analysis and conventional 2-dimensional densitometry. The hypometabolic area analyzed using 3-dimensional analysis and the differences of optical density between normal and deaf as determined by densitometry were widest and most prominent between 4 and 8 weeks after ablation. Differences were not significant before 2 weeks or after 7 months after ablation. This result shows that the hypometabolic area becomes prominent after a critical period and it decreases as the duration of deafness increases. We believe that cross-modal plasticity may be the mechanism of changes in glucose metabolism and that this result reinforced the usefulness of evaluating hypometabolic area using FDG-PET in deaf children.

Animals↗

Information processing at a central synapse suggests a noise filter in the auditory pathway of the noctuid moth.

1. The central projections of the A1 afferent were confirmed via intracellular recording and staining with Lucifer Yellow in the pterothoracic ganglion of the noctuid moths, Agrotis infusa and Apamea amputatrix (Fig. 1). Simultaneous recordings of the A1 afferent in the tympanal nerve (extracellularly) and in the pterothoracic ganglion (intracellularly) confirm the identity of the stained receptor as being the A1 cell. 2. The major postsynaptic arborizations of interneurone 501 in the pterothoracic ganglion were also demonstrated via intracellular recording and staining (Fig. 2). Simultaneous recordings of the A1 afferent (extracellularly) and neurone 501 (intracellularly) revealed that each A1 spike evokes a constant short latency EPSP in the interneurone (Fig. 2Bi). Neurone 501 receives only monaural input from the A1 afferent on its soma side as demonstrated by electrical stimulation of each afferent nerve (Fig. 2Bii). EPSPs evoked in neurone 501 by high frequency (100 Hz) electrical stimulation of the afferent nerve did not decrement (Fig. 2Biii). These data are consistent with a monosynaptic input to neurone 501 from the A1 afferent. 3. The response of neurone 501 to a sound stimulus presented at an intensity near the upper limit of its linear response range (30 ms, 16 kHz, 80 dB SPL) was a plateau-like depolarization, with tonic spiking activity which continued beyond the end of the tone. The instantaneous spike frequency of the response was as high as 800 Hz, and was maintained at above 600 Hz for the duration of the tone (Fig. 3). 4. The relationship between the instantaneous spike frequency in the A1 afferent and that recorded simultaneously in neurone 501 is linear over the entire range of A1 spike frequencies evoked by white noise sound stimuli (Fig. 4). Similarly, the relationship between instantaneous spike frequency in the A1 afferent and the mean depolarization evoked in neurone 501 is also linear for all A1 spike frequencies tested (Fig. 5). No summation of EPSPs occurred for A1 spike frequencies below 100 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Responses of neurons in the auditory pathway of the barn owl to partially correlated binaural signals.

1. Extracellular single-unit recording in anesthetized barn owls was used to study neuronal response to dichotic stimuli of variable binaural correlation (BC). Recordings were made in the output fibers of nucleus laminaris (NL), the anterior division of the ventral lateral lemniscal nucleus (VLVa), the core of the central nucleus of the inferior colliculus (ICcC), the lateral shell of the central nucleus of the inferior colliculus (ICcLS), and the external nucleus of the inferior colliculus (ICx). 2. The response of all neurons sensitive to interaural time difference (ITD) varied with BC. The relationship between BC and impulse number fits a linear, a parabolic, or a ramp model. A linear or parabolic model fits most neurons in low-level nuclei. Higher order neurons in ICx did not respond to noise bursts with strong negative binaural correlation, creating a ramp-like response to BC. 3. A neuron's ability to detect ITD varied as a function of BC. Conversely, a neuron's response to BC changed with ITD. Neurons in NL, VLVa, and ICcC show almost periodic ITD response curves. In these neurons peaks and troughs of ITD response curves diminished as BC decreased, creating a flat ITD response when BC = 0. When BC was set to -1, the most favorable ITD became the least favorable one and vice versa. The ITD response curve of ICx neurons usually has a single dominant peak. The response of those neurons to a negatively correlated noise pair (BC = -1) showed two ITD peaks, flanking the position of the primary peak. 4. The parabolic BC response of NL neurons fits the prediction of the cross-correlation model, assuming half-wave rectification of the sound by the cochlea. Linear response is not predicted by the model. However, the parabolic and the linear neurons probably do not belong to two distinct groups as the difference between them is not statistically significant. Thus, the cross-correlation model provides a good description of the binaural response not only in NL but also in VLVa and ICcC. 5. Almost all ramp neurons occurred in either ICx or ICcLS where neurons are more broadly tuned to frequency than those in the lower nuclei. The synthesis of this response type requires, however, not only the convergence of different frequency channels but also inhibition between different ITD channels. We modeled the ramp response as a three-step process. First, different spectral channels converge to create broad frequency tuning. The response to variation in BC will be linear (or parabolic) because it is a sum of linear (parabolic) responses. Second, the activity in some adjacent ITD channels is subtracted by lateral inhibition. Finally, the result is rectified using a high threshold to avoid negative activity.

Acoustic Stimulation↗

Visual behaviour mediated by retinal projections directed to the auditory pathway.

An unresolved issue in cortical development concerns the relative contributions of intrinsic and extrinsic factors to the functional specification of different cortical areas. Ferrets in which retinal projections are redirected neonatally to the auditory thalamus have visually responsive cells in auditory thalamus and cortex, form a retinotopic map in auditory cortex and have visual receptive field properties in auditory cortex that are typical of cells in visual cortex. Here we report that this cross-modal projection and its representation in auditory cortex can mediate visual behaviour. When light stimuli are presented in the portion of the visual field that is 'seen' only by this projection, 'rewired' ferrets respond as though they perceive the stimuli to be visual rather than auditory. Thus the perceptual modality of a neocortical region is instructed to a significant extent by its extrinsic inputs. In addition, gratings of different spatial frequencies can be discriminated by the rewired pathway, although the grating acuity is lower than that of the normal visual pathway.

Animals↗

Binaural characteristics of units in the owl's brainstem auditory pathway: precursors of restricted spatial receptive fields.

The barn owl uses binaural phase and intensity differences for sound localization. These two cues also determine the receptive fields of specialized neurons in the inferior colliculus. The main aim of this study was to investigate where neuronal sensitivity to the binaural cues emerges in the brainstem auditory nuclei, and how this sensitivity reaches the neurons in the inferior colliculus. The owl's phase-sensitive neurons are selective to microsecond phase differences of high frequency signals, unlike mammalian phase-sensitive neurons which are restricted to low frequency signals. In certain nuclei virtually all of the neurons are sensitive to either phase differences or intensity differences, but not to both. These nuclei form two distinctly separate pathways that converge at the inferior colliculus where neurons selective to both phase and intensity differences occur. In contrast to the mammalian auditory system, the owl's phase- and intensity difference-sensitive pathways are not segregated into low frequency and high frequency channels.

Acoustic Stimulation↗

Contact call-driven Zenk protein induction and habituation in telencephalic auditory pathways in the Budgerigar (Melopsittacus undulatus): implications for understanding vocal learning processes.

Expression of the immediate early gene protein Zenk (zif 268, egr-1, NGF1A, Krox24) was induced in forebrain auditory nuclei in a vocal learning parrot species, the budgerigar (Melopsittacus undulatus), when the subjects either listened to playbacks of an unfamiliar contact call or to a contact call with which they had been familiarized previously. Auditory nuclei included the Field L complex (L1, L2a, and L3), the neostriatum intermedium pars ventrolateralis (NIVL), the neostriatum adjacent to caudal nucleus basalis (peri-basalis or pBas), an area in the frontal lateral neostriatum (NFl), the supracentral nucleus of the lateral neostriatum (NLs), and the ventromedial hyperstriatum ventrale (HVvm). The latter three nuclei are main sources of auditory input to the vocal system. Two patterns of nuclear staining were induced by contact call stimulation-staining throughout cell nuclei, which was exhibited by at least some neurons in all areas examined except L2a and perinucleolar staining, which was the only kind of staining exhibited in field L2a. The different patterns of Zenk staining indicate that auditory stimulation may regulate the Zenk-dependent transcription of different subsets of genes in different auditory nuclei. The numbers of neurons expressing Zenk staining increased from seven- to 43-fold over control levels when the birds listened to a repeating unfamiliar call. Familiarization of the subjects with the call stimulus, through repeated playbacks, greatly reduced the induction of Zenk expression to the call when it was presented again after an intervening 24-h interval. To determine if neurons exhibiting contact call-driven Zenk expression project to the vocal control system, call stimulation was coupled with dextran amines pathway tracing. The results indicated that tracer injections in the vocal nucleus HVo (oval nucleus of the hyperstriatum ventrale), in fields lateral to HVo and in NLs labeled many Zenk-positive neurons in HVvm, NFl, and NLs. These results support the idea that, in these neurons, egr-1 couples auditory stimulation to the synthesis of proteins involved in either the storing of new perceptual engrams for vocal learning or the processing of novel and/or meaningful acoustic stimuli related to vocal learning or the context in which it occurs.

Animal Communication↗

Lateralization of dichotic speech stimuli is based on specific auditory pathway interactions: neuromagnetic evidence.

Dichotic listening (DL) is a neuropsychological technique for the study of functional laterality. Based on behavioral patient studies, the "structural theory" states that lateralization of the auditory input during DL is allowed by an inhibition of the ipsilateral pathways. We aimed here at extending this theory to provide a neurophysiological basis of verbal DL. We investigated the magnetic responses of the primary auditory cortices elicited by dichotic consonant-vowel syllables. Dichotic stimuli consisted of 2 syllables pairs, a "competing" one composed by syllables with high spectral overlap (/da/ and /ba/) and a "noncompeting" pair (/da/ and /ka/). One of the syllables in each pair was delivered at 2 intensities, whereas the other did not change. A reduced increase of source intensity in response to dichotic pairs at the 2 levels was assumed to indicate pathway inhibition effects. We obtained that the left ipsilateral pathway (i.e., the left ipsilateral signal) was strongly inhibited by the right contralateral one. Conversely, the right ipsilateral pathway did not show an inhibition larger than the left contralateral one. These results extend the notion of auditory functional asymmetries by showing that beyond hemispheric functional specialization there is an asymmetry within the ascending auditory system, which is based on a competition mechanism. The larger the competition between the left and right ear stimuli, the larger are the inhibition effects, which determine the pathway asymmetry. These findings represent as well a neurophysiological basis for the "structural theory" explaining the right ear preference usually found in verbal DL tasks.

Adult↗