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Assessment of functional integrity of brain stem auditory pathways by stimulus stress.

The effect of increasing the repetition rate of click stimuli on auditory brain stem responses has been studied in young subjects with normal hearing, in old people and in patients with multiple sclerosis. The most conspicuous effects have been observed in the amplitude of the responses, especially waves II and V, and in the value of the brain stem conduction time. Increased stimulation rates may serve as a method for the assessment of the functional status of the lower auditory pathways in diverse pathological conditions.

Acoustic Stimulation

Latency in the ascending auditory pathway determined using continuous sounds: comparison between transient and envelope latency.

The gross responses from the cochlea (round window) and two nuclei of the ascending auditory pathway of the rat in response to tone and noise bursts (compound action potentials) were compared with those recorded in response to continuous tones and noise that was amplitude modulated with pseudorandom noise. The cross-correlation function between: (1) the averaged response to the sounds that were amplitude modulated with the pseudorandom noise, and (2) one period of the pseudorandom noise, were obtained. The compound action potentials and the cross-correlation functions both had a series of peaks. The two functions had a similar morphology. The latency of the peaks in the cross-correlation showed less dependence on sound intensity than did the latency of the peaks in the compound action potentials.

Animals

A sexually dimorphic vasopressin innervation of auditory pathways in the guinea pig brain.

Vasopressin-like immunoreactivity was detected in the auditory brainstem of female guinea pigs. Stained cell bodies and fibres were found in the inferior colliculus and in the ventral trapezoid body, and immunoreactive fibres in the dorsal cochlear nucleus. No vasopressin immunoreactivity was detected in the auditory brainstem of male guinea pigs. Using oxytocin antisera we found neither immunoreactive perikarya nor fibres in the auditory pathways of guinea pigs of both sexes.

Animals

Auditory pathways in the budgerigar. I. Thalamo-telencephalic projections.

Thalamo-telencephalic auditory pathways in the budgerigar (Melopsittacus undulatus) were studied using horseradish peroxidase (HRP) histochemistry and amino acids autoradiography. The results indicate that in this species the thalamic auditory relay nucleus, n. ovoidalis, projects upon a circumscribed region of the caudal and caudomedial neostriatum including field 'L' and immediately adjacent portions of the neostriatum intermedium, pars dorsolateralis (NIDL). This region of NIDL also receives inputs from another thalamic nucleus, n. dorsolateralis posterior (DLP). In the DLP is in receipt of tectal inputs. Projections of DLP upon NIDL were confirmed with amino acids autoradiography. The results of the HRP experiments indicate that different portions of n. ovoidalis project upon different portions of field 'L' and NIDL. Neurons in the dorsal and lateral portions of the n. ovoidalis project upon more medial portions of field 'L'. Neurons located centrally in the n. ovoidalis project upon central and lateral portions of field 'L'. Neurons in the ventromedial portion of the n. ovoidalis are labeled in all cases in which HRP is placed in either field 'L' or in the DLP projection field immediately adjacent to field 'L' proper. HRP injections placed in NIDL lateral to the projection fields of the n. ovoidalis and DLP label neurons within other diencephalic nuclei including the n. subrotundus. The caudal and intermediate levels of the neostriatum intermedium apparently serve as a complex processing area for many thalamic inputs in this species. The existence of multiple ascending thalamo-telencephalic projections from portions of the thalamus receiving inputs from both the visual (i.e., tectal) and auditory (i.e., n. mesencephalicus lateralis pars dorsalis) portions of the midbrain roof (i.e., from DLP and from n. ovoidalis) suggests the possibility that intermodal associations may take place in these telencephalic fields. Such partially converging pathways may provide a basics for intermodal associations which are important in individual recognition and social signalling systems in this species.

Animals

An EM study of the dorsal nucleus of the lateral lemniscus: inhibitory, commissural, synaptic connections between ascending auditory pathways.

The dorsal nucleus of the lateral lemniscus (DNLL) and its connections constitute one of the ascending auditory pathways to the inferior colliculus. One notable feature of this nucleus is the heavy commissural connections between DNLL on opposite sides of the midbrain. These commissural connections may have a significant impact on the ascending pathway. In this study, the fine structure of DNLL in the cat and its commissural connections were examined. Both anterograde and retrograde transport methods were used simultaneously at the EM level. Injections of 3H-leucine mixed with WGA-HRP were made in one DNLL. After axonal transport, EM autoradiographic methods were used to identify the anterogradely labeled axonal endings from the opposite DNLL. In the same location, retrogradely labeled neurons with crossed connections were identified with HRP histochemistry. Two types of axonal endings were found in DNLL, those with round synaptic vesicles forming asymmetrical synaptic junctions and those with pleomorphic vesicles and symmetrical synapses. Both types were equally common. However, only endings with pleomorphic vesicles were labeled after injections in the contralateral DNLL. The labeled endings from the opposite DNLL appeared to represent a homogeneous population, even though a number of variations in the 2 types of endings were found. Labeled endings were presynaptic to all parts of neurons in DNLL, but a large proportion of the synapses were on cell bodies and large dendrites. Two patterns of nuclear morphology and distribution of rough endoplasmic reticulum were identified and may represent different cell types. Examples of both cell types were observed to project to the contralateral side and received labeled synaptic endings. The major finding of this study is that the crossed connections between DNLL exhibit the morphology associated with inhibitory function. Since neurons in DNLL are thought to use GABA as a neurotransmitter, the crossed connections could provide inhibitory inputs to DNLL on each side. Since some neurons receive numerous axosomatic inputs from the contralateral DNLL and also project to the opposite side, they may participate in direct reciprocal, inhibitory connections between the nuclei. Crossed inhibitory connections in the DNLL pathway may be important in regulating the flow of ascending auditory information.

Animals

Effectiveness of middle ear electrical stimulation for activating central auditory pathways.

Electrical stimulation of afferent auditory elements through electrodes placed in the middle ear was investigated in acute guinea pig preparations. Thresholds for auditory activation were current dependent for low frequencies (less than 1 kHz) and charge-dependent at higher frequencies. Threshold currents were 3-5 times those for intracochlear stimulation. Mechanisms of activation were examined with removal of cochlear fluids and injection of neomycin, Xylocaine, saline, and artificial perilymph with different calcium concentrations. Neurons of the spiral ganglion are indicated as mediators of this stimulation.

Animals

Time of origin of neurons of the rat inferior colliculus and the relations between cytogenesis and tonotopic order in the auditory pathway.

Groups of pregnant rats were injected with two successive daily doses of 3H-thymidine from gestational day 12 and 13 (E12+13) until the day before parturition (E21+22) in order to label in their embryos the proliferating precursors of neurons. At 60 days of age the proportion of neurons generated (or no longer labelled) on specific embryonic days was determined quantitatively in six vertical strips of the inferior colliculus. It was established that the neurons of the inferior colliculus are produced between days E14 and the perinatal period in an orderly sequence: the earliest generated cells are situated rostrally, laterally and ventrally in the principal nucleus, the latest generated cells are situated caudally, medially and dorsally in the pericentral nucleus. This cytogenetic gradient suggested that the cells are produced dorsally in the caudal recess of the embryonic aqueduct and are deployed in an "outside-in" pattern. This study has brought to a conclusion our datings of neuron production in the central auditory pathway of the rat. The results revealed that in those structures in which a cytogenetic gradient could be recognized, the orientation of this gradient and the regional tonotopic order (demonstrated mostly in species other than the rat) tended to be aligned. Moreover, with the exception of the medial trapezoid nucleus and the dorsal nucleus of the lateral lemniscus (which receive contralateral input from the cochlear nuclei), sites with early-produced neurons correlated with units responding preferentially to high frequency tones and vice versa. This suggested that the orderly production of neurons within different components of the auditory system is a factor in their subsequent topographic organization. A comparison of the temporal order of neuron production in different components of the auditory pathway suggested that the establishment of orderly topographic relations between some of the structures (e.g., the medial geniculate body and the primary auditory cortex) takes place before this spatial relationship could be specified as a cochleotopic order.

Animals

The central auditory pathway of the gerbil Psammomys obesus: a deoxyglucose study.

The tonotopic organization of the central auditory pathway of the gerbil Psammomys obesus was mapped with deoxyglucose autoradiography under anesthesia. Animals, injected with tritiated deoxyglucose, were stimulated with 0.8, 2.5 and 17.0 kHz tone bursts monaurally in the free field and compared with non-stimulated controls. Apart from the medial geniculate body, all auditory structures showed sound-specific uptake of tracer. Frequency selective tracer accumulation could not be discriminated in the auditory cortex, the nuclei of the lateral lemniscus or the superior olivary complex. Isofrequency laminae could be determined most precisely in the dorsal cochlear nucleus and the central nucleus of the inferior colliculus. About half the mass of each of these nuclei is devoted to the processing of sound below 2.5 kHz. This disproportionately large representation of low frequencies matches the very high sensitivity of the peripheral auditory system in that range.

Acoustic Stimulation

[Influence of acoustic stimulation in the maturation of the auditory pathway].

The aim of this study is to analyze the relationship between age and the maturational changes occurring in the peripherical auditory system and the influence of the acoustic stimulation. With this purpose Auditory Brainstem Responses (ABR) were recorded at the 35 and 39 weeks gestational age, in 56 ears of 28 premature infants. The ABR were analyzed the changes in latency values of the I, V waves and I-V intervals. In order to know the influence of the acoustic stimulation on the development of auditory pathway, we made 2 groups with the 28 premature children, one of them control group and the other stimulated with maternal voice from 35 till 39 weeks. The stimulated group had one maturate auditory evoked responses at 39 weeks gestational age. Showing a latency decrease wave V and I-V interval, compared to control group.

Acoustic Stimulation

Central acoustic tract in an echolocating bat: an extralemniscal auditory pathway to the thalamus.

To determine the sources and targets of auditory pathways that bypass the inferior colliculus in the mustache bat, we injected WGA-HRP in the medial geniculate body and related auditory nuclei of the thalamus as well as in the lower brainstem. We used electrophysiological methods to verify that the injection electrode was in an area responsive to sound. The only thalamic injections that produced retrograde transport to cells in auditory nuclei caudal to the inferior colliculus were those that included the suprageniculate nucleus. These injections labeled a group of large multipolar cells lying between the ventral nucleus of the lateral lemniscus and the superior olivary complex. Neurons in this cell group have also been shown to project to the deep layers of the superior colliculus in the mustache bat. The pathway revealed by these studies is almost identical to the "central acoustic tract" in which fibers course medial to the lateral lemniscus and bypass the inferior colliculus to reach the deep superior colliculus and the suprageniculate nucleus.

Animals

Auditory pathways to the cortex in Tupaia glis.

The auditory system of the tree shrew, Tupaia glis, was investigated by identifying axonal degeneration after lesions of the lateral lemniscus, the inferior colliculus, the medial geniculate nucleus and the auditory cortex. The results show that the lateral lemniscus projects to the central nucleus of the inferior colliculus which in turn projects principally to the ventral division of the medial geniculate nucleus but to a lesser extent to the magnocellular division of the medial geniculate nucleus. The final step in the pathway to the cortex is achieved by a projection from the ventral division to the fourth layer of auditory koniocortex. There appear to be several auditory pathways parallel to this primary path. The lateral lemniscus projects to the dorsal division of the medial geniculate nucleus; the deeper layers of the superior colliculus project to the posterior nucleus; and both the dorsal division and the posterior nucleus project to the belt caudal to auditory koniocortex. The caudal division of the medial geniculate nucleus may constitute a relay in still another path from the pericentral division of the inferior colliculus. Finally, the magnocellular division also appears to be distinct insofar as its cortical projections are confined chiefly to the deeper layers. A comparison between the tree shrew and the cat reveals a similar organization in the two species. In the cat the starting point for understanding the organization of the several auditory pathways is the distinction between a core cortical zone which corresponds to konicortex and to AI and a peripheral belt. The core receives essential projections from the ventral division; the belt receives sustaining projections from the cell groups which surround the ventral division. It is reasonable to hypothesize that this difference between the core and the belt is characteristic of all mammals.

Animals

Distribution of GABAergic perikarya and terminals in the centers of the higher auditory pathway of the chicken.

The distribution of presumed GABAergic neurons and axon terminals in nuclei of the higher auditory pathway of the chicken was investigated by immunocyto-chemical methods employing antisera to the rate-limiting enzyme of GABA synthesis, glutamic acid decarboxylase, and to GABA. In the mesencephalic auditory center (MLD) about 20% of the cells reveal immunoreactivity. In contrast, the thalamic relay station nucleus ovoidalis is devoid of immunostained somata. This nucleus contains a high density of punctate immunoreactive structures presumed to be GABAergic axon terminals. In the auditory forebrain center field L and the auditory portions of the hyperstriatum ventrale, up to 8% of the cells were immunopositive. These neurons were significantly smaller than estimated from measurements of the overall cell population in these nuclei. From the two-dimensional arrangement of immunopositive neurons it is suggested that the GABAergic system in the avian auditory telencephalon consists of two separate groups of neurons: one subgroup mediating local inhibitory interactions, the other responsible for lateral inhibition between different frequency representations.

Animals

Neonatal cochlear hearing loss results in developmental abnormalities of the central auditory pathways.

We have used animal models of long term neonatal cochlear hearing loss to study developmental plasticity of the central auditory pathways. Newborn chinchilla pups and feline kittens were treated with the ototoxic drug amikacin, so as to induce basal lesions in the cochlea. At maturity these animals were used in single unit electrophysiological mapping studies, in which the cochleotopic organization of primary auditory cortex (of the cat) and the inferior colliculus of the midbrain (in the chinchilla) were mapped. We have observed, both in the midbrain and auditory cortex, massive reorganization of frequency representation. Most striking were the presence of large monotonic regions (i.e. large areas in which all neurons have similar tuning properties). Cochlear lesions which involve inner hair cells clearly modify the normal development of cochleotopic representation in the midbrain and cortical regions. We suggest that similar abnormal patterns of frequency representation will exist in human subjects with long term neonatal hearing loss.

Amikacin

[Anatomy of the central auditory pathway. Demonstration with horseradish peroxidase in the guinea pig].

The neurones of the afferent and efferent auditory pathways were labelled by axonally transported horseradish peroxidase. The first neurone of the ascending system is the acoustic nerve with the spiral ganglion. These fibres terminate mainly in the ventral cochlear nucleus (VCN). The neurones of the latter chiefly run to the contralateral superior olivary complex (SOC), whereas the neurones of the dorsal cochlear nucleus (DCN) terminate mainly in the central nucleus of the contralateral inferior colliculus (IC). The nerve cells of the superior olivary complex and nuclei of the lateral lemniscus (DLL, VLL) project to the IC. The IC neurones run mainly uncrossed to the medial geniculate body (MGB), i.e. the neurones of the central nucleus of the inferior colliculus terminate in the ventral nucleus of the medial geniculate body. This latter nucleus projects to the primary region A I of the auditory cortex, whereas the neurones in the pericentral medial geniculate body terminate in the associated auditory regions A II, EP and SF. The auditory areas of both hemispheres is well interconnected by commissural fibres. In addition to this ascending pathway there is a descending system. The parent cells correspond to pyramidal neurones in layer V in the auditory cortex. These neurones terminate in the medial geniculate body and in the pericentral nuclei of the inferior colliculus. From this, efferent neurones project to the DCN and SOC. The neurones of the olivocochlear bundles originate in the SOC; these bundles terminate predominantly on the surface of the outer hair cells in the organ of Corti.

Animals

Visual projections induced into the auditory pathway of ferrets. I. Novel inputs to primary auditory cortex (AI) from the LP/pulvinar complex and the topography of the MGN-AI projection.

The organization of cortical circuitry responsible for processing sensory information is a subject of intense examination. However, it is not known whether cortical cells in different sensory cortices process information in a way that is specific to the modality of their input, or whether there are commonalities in processing circuitry across different cortices. In our laboratory, this question has been investigated at the level of the geniculocortical pathway by routing information of one sensory modality into the processing circuitry of another modality. Appropriate early lesions cause growth of retinal axons into the auditory thalamus (MGN) (Sur et al., Science 242:1437, '88). Previously, we have established that the MGN carries the resulting visual information on to primary auditory cortex (AI), which thus contains visually responsive neurons and a topographic representation of the retina (Roe et al., Soc. Neurosci. Abstr. 14:460, '88; Sur et al., Science 242:1437, '88). In this paper, we describe anomalous projections from the dorsal part of the thalamus, specifically the lateral posterior/pulvinar complex, into AI. This result demonstrates that thalamic neurons belonging to one modality can be induced to project to cortex that is normally of a different modality. In addition, we have studied in detail the nature of the MGN to AI projection in these animals as compared to the normal projection. The MGN to AI projection appears to be unaltered by the lesions; the location and topography of labelled cells are similar to that in normal animals. Because the MGN to AI projection is still highly divergent along the "isofrequency" dimension when compared to the tonotopic dimension, our data suggest that visual topography in the cortical map is created within the auditory cortex, perhaps by activity-dependent sharpening of the retinal representation during development.

Animals

Calcitonin-gene related peptide is an evolutionarily conserved marker within the amniote thalamo-telencephalic auditory pathway.

The distribution of neurons and fibers containing calcitonin-gene-related peptide (CGRP) was mapped in the thalamo-telencephalic auditory pathways of four amniote species, rats, pigeons (Columba livia), caiman (Caiman crocodilus), and turtles (Pseudemys scripta). In colchicine-treated turtles and pigeons, numerous CGRP+ perikarya were observed in the auditory relay nucleus of the thalamus (n. reuniens of reptiles, and n. ovoidalis of birds). In pigeons, these neurons were most abundant in the outer circumference of the nucleus and were not observed without colchicine pretreatment. In the telencephalon of turtles, caiman, and pigeons, CGRP+ fibers were observed within portions of the dorsal ventricular ridge previously shown to receive projections from the auditory thalamus, thus implying that the thalamic CGRP+ neurons observed here in fact project to these telencephalic areas. In colchicine treated rats, numerous CGRP+ perikarya were observed along the ventral margin of the medial geniculate nucleus extending into the posterior intralaminar and peripeduncular nuclei, as well as occasionally within the ventral subdivision of the medial geniculate nucleus. Injections of fluorogold into the auditory cortex combined with immunofluorescence labeling for CGRP revealed that CGRP+ cells in these areas do, in fact, project to the auditory cortices. The present results are interpreted as providing strong support for the theory, advanced previously, that the medial geniculate nucleus of mammals, nucleus ovoidalis of birds, and nucleus reuniens of reptiles contain at least some homologous cell populations. Although the data are consistent with the theory that the telencephalic projection fields are homologous, other interpretations are also consistent with the data presented here. These include the possibility that auditory thalamic projections to the telencephalon arose independently in the lines of evolution leading to mammals and sauropsids.

Alligators and Crocodiles

Functional anatomy of forebrain auditory pathways in the budgerigar (Melopsittacus undulatus).

Interconnections of forebrain auditory and vocal control nuclei were mapped in the budgerigar using pathway tracing techniques. The anatomical results indicate four circuits by which auditory information may influence the vocal motor system: (1) direct auditory thalamic projections from nucleus dorsomedialis posterior (DMP) to both the neostriatal higher vocal center (HVC) and robust archistriatal nucleus (RA); (2) direct projections from a neostriatal projection field of DMP (i.e., MAN, the magnocellular nucleus of the neostriatum) to HVC and RA; (3) projections from DMP and other 'accessory' auditory thalamic nuclei to the ventral paleostriatum (VP), which in turn projects to MAN and RA; (4) projections to HVC from the lateral hyperstriatum ventrale (HV), which receives input from nucleus basalis (Bas) as well as from the oval nucleus of the HV (HVo), which receives direct input from RA. Lesion methods were used to evaluate the roles of auditory pathways in call learning and production. The results show that pathways associated with Bas are essential for call production in both adult and unfledged budgerigars, while VP efferents influence vocalization only in young, unfledged budgerigars. Lesions centered in either the primary auditory neostriatum (Field L2a) or the neostriatal area in receipt of Field L input (the ventrolateral neostriatum intermedium or NIVL) did not affect vocalization in juvenile or adult budgerigars.

Animals