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T N Parks

Publications and source records attributed to T N Parks.

54 records · Page 3Linked to original sources

Non-N-methyl-D-aspartate receptors mediating synaptic transmission in the avian cochlear nucleus: effects of kynurenic acid, dipicolinic acid and streptomycin.

We have examined the effects of a number of excitatory amino acid antagonists on transmission at the cochlear nerve-nucleus magnocellularis synapse in the chicken. Using an in vitro preparation and bath application of drugs, we studied the effects of kynurenic acid and several related substances, streptomycin and a selective N-methyl-D-aspartate receptor antagonist, DL-alpha-aminosuberate. The last compound had no effect on evoked transmission. Of the various kynurenic acid-related compounds tested, only kynurenic and dipicolinic acid selectively altered responses in nucleus magnocellularis. Quinolinic acid, a kynurenic acid analogue that is structurally akin to dipicolinic acid but which acts selectively at N-methyl-D-aspartate receptors, was without effect. The effect of kynurenic acid was solely inhibitory, completely blocking postsynaptic responses with a potency dependent on the frequency of nerve stimulation. No such frequency dependence was seen with dipicolinic acid although this compound also completely suppressed evoked responses. In addition dipicolinic acid potentiated postsynaptic responses at concentrations only slightly lower than those causing inhibition. Streptomycin inhibited responses in nucleus magnocellularis but this effect seems to result partially from the ability of the drug to inhibit presynaptic calcium influx. Our finding that selective antagonists of N-methyl-D-aspartate receptors were ineffective while antagonists of both receptor types, such as kynurenic and dipicolinic acids, inhibited evoked responses reinforces the conclusion that postsynaptic receptors mediating transmission at this synapse are of the non-N-methyl-D-aspartate type [Nemeth et al. (1983) Neurosci. Lett. 40, 39-44].(ABSTRACT TRUNCATED AT 250 WORDS)

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A developmental gradient of dendritic loss in the avian cochlear nucleus occurring independently of primary afferents.

Cochlear nerve axons and their target neurons in nucleus magnocellularis (NM) of the chicken undergo extensive parallel structural transformations during development. Between embryonic days 12 and 17 (E12-E17), each immature highly branched axon condenses into a mature calyxlike ending applied to a single NM neuron. Simultaneously, NM neurons are transformed from multipolar cells with many long dendrites into spherical unipolar neurons with only an axon. We tested the hypothesis that cochlear nerve input is necessary for the transformation of NM cells by surgically destroying one otocyst on E3, thereby preventing formation of the nerve. Nucleus magnocellularis neurons from embryos at E11-E12, E13-14, and E17-18 were stained by horseradish peroxidase injected into their axons or by a Golgi-Hortega method. In camera lucida drawings, the number of dendrites on each cell was counted and the cell's position along the posterior-to-anterior and lateral-to-medial axes of the nucleus quantified. At E11-12, neurons throughout NM on both the deafferented and normally innervated sides of the brain have about ten dendrites. At E13-14, there is a steep spatial gradient in dendritic number bilaterally; cells at anteromedial positions have about two dendrites, while cells in posterolateral positions have an average of nine dendrites. By E17-18, only 14% of the neurons on either side have a dendrite, and these cells are evenly distributed throughout the nucleus. We conclude that cochlear nerve axons are not required for normal spatio-temporal gradients of dendritic loss, even though the absence of these axons causes severe atrophic changes in NM.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Auditory brainstem anomalies in albino cats: II. Neuronal atrophy in the superior olive.

In a previous paper (Brain Res., 260:1-9, 1983) we reported that albino cats show abnormal auditory brainstem evoked responses that appear to arise from structural defects in or near the superior olivary complex. In the present study, neuronal cross-sectional area in brainstem nuclei was compared in albino and normally pigmented adult cats. The albinos were true tyrosinase-negative (cc) and should not be confused with the deaf white cat (W); the albinos are not deaf. Neurons in the medial superior olivary nucleus (MSO) of albinos were, on average, 41% smaller than in pigmented animals; there was no overlap in the neuronal size distributions for the two groups of animals. Cell size in the lateral superior olive, medial nucleus of the trapezoid body, ventral nucleus of the lateral lemniscus, anteroventral cochlear nucleus, dorsal cochlear nucleus, and facial nucleus was also smaller (by 9-21%) in albinos than in pigmented animals but none of these differences was statistically reliable. In the abducens nucleus, neurons were 12% larger in albinos than in pigmented animals, demonstrating that neuronal size in the albinos is not uniformly smaller. Several lines of evidence suggest that the auditory system defects in albinos are related to abnormal pigmentation rather than to other gene effects. It is possible that a subtle pigment-related disruption of inner ear development in albinos results in a central cascade of atrophic changes along the auditory pathway.

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Pharmacologic evidence for synaptic transmission mediated by non-N-methyl-D-aspartate receptors in the avian cochlear nucleus.

The hypothesis that synaptic transmission between the auditory nerve and the cochlear nucleus is mediated by an excitatory amino acid acting through N-methyl-D-aspartate (NMDA) receptors was examined in an in vitro preparation of the chicken brainstem. The ability of various bath-applied excitatory amino acid receptor antagonists to inhibit synaptically-evoked responses was assessed by recording field potentials from nucleus magnocellularis (NM) following electrical stimulation of the cochlear nerve. Antagonists that selectively block responses mediated by NMDA receptors, such as D-alpha-aminoadipate and 2-amino-5-phosphonovalerate, were without effect on evoked transmission in NM. In contrast, antagonists that additionally act on non-NMDA receptors, such as cis-2,3-piperidine dicarboxylate and gamma-D-glutamylglycine, reversibly suppressed transmission. The results indicate that (1) transmission in the chicken auditory system is mediated by non-NMDA receptors, and (2) a substance(s) chemically akin to aspartate and glutamate may be the transmitter used by the auditory nerve in NM.

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Morphology and origin of axonal endings in nucleus laminaris of the chicken.

The axonal endings on the somata and dendrites of third-order auditory neurons in nucleus laminaris (NL) were measured and classified in thin-sectioned material from adult chickens. Two methods were used to determine which ending types arise from second-order auditory neurons in nucleus magnocellularis (NM): 1) degeneration of axonal endings in NL after transection of the crossed dorsal cochlear tract (CTrX) carrying the axons of each NM to the contralateral NL, and 2) injection of horseradish peroxidase (HRP) into NM or the CTrX to label endings in NL by anterograde transport. About 42% of the perikaryl surface of NL neurons and 63% of the dendritic surface are apposed by axon terminals arising from NM; these endings are also prevalent on the axon hillock and initial segment. The NM endings are characterized by round, clear synaptic vesicles distributed at an average density of 76/microns2 behind small punctate synaptic junctions with thick synaptic densities. These endings degenerate preferentially after transection of the CTrX and are the only endings consistently labeled after HRP injections. About 31% of the perikaryl surface of NL and 10% of the distal dendritic surface are apposed by a prominent non-NM axonal ending type. This ending is characterized by a synaptic vesicle density of 135/microns2 and a single large area of synaptic contact which bears very slight densities on both pre- and postsynaptic membranes. On the perikaryon, about 80% of these non-NM terminals end on the cell body proper, with the rest found on proximal dendrites or capping the short somatic processes or spines occasionally seen in NL. The distribution of the two ending types does not differ significantly along the posterior-to-anterior axis of NL.

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Auditory brainstem anomalies in albino cats. I. Evoked potential studies.

The amount of melanin pigmentation in the inner ear is positively correlated with the general pigmentation of the body and specifically with the amount of pigment in the eye. The misrouting of retinofugal projections which accompanies ocular and oculocutaneous albinism has been thought to be a defect in decussation unique to the visual system. Evidence suggests that functional abnormalities may also exist in the auditory systems of albino humans and animals. To evaluate this possibility, evoked potential techniques were used to examine the functional anatomy of decussating brainstem auditory pathways in albino and pigmented cats. Auditory brainstem responses (ABRs) were recorded from albino, pigmented, and Siamese cats using monaural stimulation. ABRs were recorded ipsilateral and contralateral to the stimulated ear. The albinos were complete tyrosinase-negative (cc), not the dominant white (W) variety associated with deafness. In pigmented cats, the amplitudes of ABRs recorded with the reference electrode ipsilateral to the stimulated ear and the ABRs recorded using the reference contralateral to the stimulated ear did not differ by more than 40% for individual components appearing between 2 and 4 ms after stimulus onset. In albino cats the components at these latencies were obliterated or greatly attenuated in the ABR recorded using the reference contralateral to the stimulated ear. These data indicate that anomalies may exist in the brainstem at the level of the acoustic striae, superior olivary nuclei and/or trapezoid body in tyrosinase-negative albino cats.

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Functional synapse elimination in the developing avian cochlear nucleus with simultaneous reduction in cochlear nerve axon branching.

We studied the chick auditory system to determine whether there is a normal developmental reduction in the number of cochlear nerve axons innervating individual cochlear nucleus (nucleus magnocellularis, NM) neurons. We also examined the preterminal branching patterns of cochlear nerve axons during development. The number of cochlear nerve axons innervating individual NM neurons was estimated by counting the increments in the postsynaptic response as the intensity of cochlear nerve electrical stimulation was varied gradually; this number fell from a mean of 4.0 on embryonic day 13 (E13) to a mean of 2.2 on E17 and E18 and the 4th day after hatching. This highly reliable decline in functional convergence was accompanied by a decrease in the number of preterminal branches of cochlear nerve fibers innervating the NM. On E13 and E14, most axons stained by iontophoretic injections of horseradish peroxidase showed two distinct preterminal branches in the NM. By E17 and E18 and thereafter, cochlear nerve axons were unbranched and terminated with a characteristic single large calycine ending in the NM. There are about twice as many cochlear nerve axons as neurons in the NM and the number of fibers in the nerve appears to decline only slightly between E13 and E17. The 50% decline in the number of cochlear nerve axons making functional synapses on individual NM neurons therefore is associated principally with the concurrent elimination of cochlear nerve axon branching in the NM.

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Morphology of axosomatic endings in an avian cochlear nucleus: nucleus magnocellularis of the chicken.

The axonal endings formed on the somata of neurons in the brainstem auditory nucleus magnocellularis (NM) were measured and classified in thin-sectioned material from adult chickens. Degeneration of primary endings after destruction of the basilar papilla and labeling of cochlear nerve fibers by injection of horseradish peroxidase (HRP) into the inner ear were used to determine which ending types arise from the cochlear ganglion. About 60% of the perikaryal surface is apposed by primary type terminals. These primary endbulbs are characterized by round clear synaptic vesicles distributed at an average density of 63 vesicles/micrometers 2 and a number of small, punctate, highly asymmetrical synaptic contacts. The primary type is the only class of endings which disappears after destruction of the basilar papilla and which is consistently labeled after HRP injections into the ear. These endings probably account for the "fast" EPSP seen in NM during stimulation of the cochlear nerve. NM neurons receive two types of nonprimary ending. About 13% of the perikaryal surface is apposed by a morphologically homogeneous class of small "symmetrical" endings; these are characterized by a flattened rhomboidal shape, numerous mitochondria, frequent coated vesicles, and small round or ovoid synaptic vesicles at an average density of 165 vesicles/micrometers 2. Most of the length of the apposition between ending and cell body is occupied by a synaptic complex with thin symmetrical presynaptic and postsynaptic densities. These endings were frequently found on short somatic processes. The second nonprimary axosomatic ending type in NM is most easily identified in experimental material; these endings occupy about 5% of the cell surface area and have a distinctly rounded profile in cross section. These endings typically exhibit clear round synaptic vesicles at a density of 111 vesicles/micrometers 2 arrayed before synaptic contacts which occupy a substantially larger fraction of the total apposition length than in the endbulbs. Many of these synaptic contacts show well-defined presynaptic grids and have postsynaptic densities intermediate in width between the endbulbs and the symmetrical endings. This second type of nonprimary ending may be responsible for the long-latency excitatory post-synaptic potentials seen in intracellular recordings from NM during electrical stimulation of the cochlear nerve. The morphology and distribution of the three ending types does not differ significantly along the posterior-to-anterior axis of NM.

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Age- and position-dependent effects of monaural acoustic deprivation in nucleus magnocellularis of the chicken.

The effect of a moderately severe monaural conductive hearing loss on the development of neuronal size in the avian nucleus magnocellularis (NM) was investigated. NM is considered to be the homologue of the mammalian anteroventral cochlear nucleus and receives large calyceal synaptic endings from the cochlear nerve. Silicone plastic earplugs which produce a 40 dB broadband conductive hearing loss were placed in one external auditory canal of chick embryos on the 18th day of incubation. After hatching, all animals were housed in communal brooders and sacrificed at 4, 10, 25, and 60 days of age. Nissl-stained sections from paraffin- and plastic-embedded brains were used to sample neuronal cross-sectional areas in NM on the deprived and nondeprived sides of the brain. These samples were obtained separately in each brain from three posterior-to-anterior percentage quartiles within NM. Statistical analyses of these data showed that the severity of deprivation-induced cell size changes in NM varied as a function of both age and position. In the 4- and 10-day groups, no significant deprived-versus-nondeprived differences in neuronal size were seen in any area of the nucleus. At 25 days after hatching, only the third posterior-to-anterior quartile (i.e., 50-74%) showed a significant difference; this difference was also significantly greater than those in the second and fourth quartiles at this age. By 60 days, all three sampled areas in NM showed highly significant differences (averaging 12%) in mean neuronal cross-sectional area. Cell size values from the deprived and nondeprived sides of 60-day-old experimental animals were also compared with values from 60-day-old control subjects. Whereas the deprived NM cells were significantly smaller than controls, there was no evidence for a reliable hypertrophy in the nondeprived cells. Thus, the principal effect of the acoustic deprivation produced was to retard continued growth of the deprived neurons after 4 days of age.

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Afferent influences on the development of the brain stem auditory nuclei of the chicken: otocyst ablation.

The effects of embryonic deafferentation on the morphological development of the avian cochlear nuclei, n. angularis (NA) and n. magnocellularis (NM), were investigated. The right otocyst was surgically removed from chick embryos at 55 to 60 hours of incubation and the subsequent development of total volume, neuron number, and neuron cross-sectional area were studied with quantitative methods in animals sacrificed at 2-day intervals between embryonic days 9 and 19 and at 28 days posthatching. The development of NA and NM is severely affected by otocyst ablation. Between embryonic days 9 and 19, a large group of NA neurons in the medioventral portion of the nucleus on the operated side moves to an ectopic ventromedial position, while the remainder of this nucleus stays in its normal dorsolateral position. Beginning about day 13 of incubation, the normal increase in the volume of NA and the size of its neurons becomes progressively retarded and 40% of its neurons are lost. The growth of NM is also retarded after day 11 of incubation and the growth of mean neuron size is retarded after day 15. There is a 30% loss of neurons in NM which begins after embryonic day 11. The results indicate the primary cochlear fibers make a critical contribution to the growth and maintenance of their target neurons. The absence of this facilitative influence following otocyst ablation becomes apparent just at the time synapses would normally be formed between the the primary auditory afferents and the brain stem auditory neurons. The abnormal movement of neurons in nucleus angularis to an ectopic position after otocyst ablation suggests that primary auditory afferents may serve to stabilize the position of their target cells within the developing brain.

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Organization and development of the brain stem auditory nuclei of the chicken: primary afferent projections.

The pattern of primary auditory projections to the brain stem of young chickens was investigated using terminal degeneration methods and orthograde transport of horseradish peroxidase (HRP) or tritiated amino acid. Of particular interest was the question of whether nucleus laminaris (NL) receives primary afferents. A study of silver-stained degeneration pattersn in nucleus magnocellularis (NM) and NL at three intervals following unilateral interruption of the cochlear nerve revealed that by 48 hours after the lesion, degenerating terminals were found only in the ipsilateral nucleus angularis (NA), NM and lagenar projection areas but not in NL. Five- and eight-day survival times, however, also revealed degeneration bilaterally in NL. The appearance of terminal degeneration in NL at the longer survival times is attributed to the previously-reported severe and rapid transneuronal degeneration of neurons in NM following deafferentation and not to the presence of cochlear nerve terminals in NL. Injection of HRP or tritiated proline into the basilar papilla produced patterns of labeling similar to that seen in the 2-day degeneration material; HRP reaction product or autoradiographic label were seen only in the ipsilateral NA and NM and in the ipsilateral projection areas of the macula lagena but not in either NL. The patterns of primary auditory projections revealed by the three methods were quite similar to each other and to that previously reported for the pigeon and confirm the conslucion that the laminar nucleus of chickens does not receive primary afferents.

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Rapid dendritic atrophy following deafferentation: an EM morphometric analysis.

The nucleus laminaris (NL), a third-order brain stem auditory nucleus in birds, receives afferents to its dorsal dendrites from the ipsilateral nucleus magnocellularis (NM), while the ventral dendrites of NL neurons are innervated by axons from the contralateral NM via the crossed dorsal cochlear tract (CTrX). The CTrx was transected in young chickens and, 96 h later, NL was examined for cytological changes. A morphometric analysis of electron micrographs from lesioned and shamd axon terminals were localized almost entirely to the ventral neuropil region of NL. (2) The volume density of dendrite in the ventral region of NL of lesioned animals was reduced by 85% compared to both the dorsal dendritic region of the same animals and the ventral dendritic region of sham-operated control animals. (3) The frequency with which primary dendrites were encountered in the ventral neuropil of lesioned animals was 81% lower than sham-operated controls. (4) Frequently, there was an apparent reduction in the amount of rough endoplasmic reticulum, Golgi apparatus and cytoplasmic granularity in the deafferented part of the NL neurons. (5) The data indicate that the cytological integrity of dendritic processes cna be specifically, profoundly and very rapidly compromised by removing a significant proportion of their afferents, suggesting that a tonic influence may be exerted by the presynaptic terminals.

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Organization and development of brain stem auditory nuclei of the chicken: tonotopic organization of n. magnocellularis and n. laminaris.

Extracellular recordings of responses to tone-burst stimulation were used to determine the tonotopic organization of n. magnocellularis (NM) and n. laminaris (NL) in hatching chickens. NM cells show "primary-like" response patterns to ipsilateral stimulation, and are arranged in dorso-ventral isofrequency columns. Units responding to the highest frequency tones (about 4,100 Hz) are situated at the rostromedial pole of the medial division. Units with lower characteristic frequencies (CF's) are found at successively caudal and lateral sites, until extremely low CF's ( less than 500 Hz) are represented dorsoventrally in the daudolateral tail of the lateral division. No evidence was found of auditory input to the region which receives projections from the macula lagena. NL receives polarized, binaural, excitatory input. Units have similar CF's and thresholds to tones presented to either ear. The tonotopic organization in NL matches that found in NM--high CF's rostromedially and low CF's caudal and lateral. Quantitative procedures were developed for relating CF to the position of a unit within either nucleus. These analyses account for 79% and 89% of the frequency variance found within NM and NL, respectively, and predict the CF of a neuron by its position within each nucleus.

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Organization and development of brain stem auditory nuclei of the chicken: organization of projections from n. magnocellularis to n. laminaris.

The tonotopic and topographic organization of the bilateral projection from second-order auditory neurons of nucleus magnocellularis (NM) to nucleus laminaris (NL) was examined in young chickens. In one group of birds, the NM axons which innvervate the contralateral NL were severed by cutting the crossed dorsal cochlear tract at the midline. Heavy terminal degeneration in NL was confined to the neuropil area immediately ventral to the perikaryl lamina. Very little degeneration was seen in the dorsal neuropil region. In a second series of animals, the charactertistic frequency (CF) of cells in an area of NM was first determined by microelectrode recording techniques and then a small electrolytic lesion was made through the recording electrode. Following survival periods of 24-48 hours, the distribution of projections from the lesioned area to the ipsilateral and contralateral NL was examined using the Fink-Heimer method. As previously described in the pigeon, projections from NM terminate densely in the neuropil region immediately dorsal to the ipsilateral NL cell bodies and ventral to the perikaryl layer on the contralateral side, providing each NL neuron with segregated binaural innervation. Lesions in any area of the NM produced degeneration confined to a limited caudo-rostral and medio-lateral portion of both laminar nuclei. To investigate this topographic relationship, the cuado-rostral extents of the lesion in NM and of the resulting degeneration in both NL were determined. Linear regression and correlation analyses then related these positional values to each other and to the CF found at the center of each lesion. All correlations were highly significant and ranged from 0.78 between the position of the lesion in NM and CF to 0.91 between the caudo-rostral position of degeneration in the NL ipsilateral and contralateral to the lesion. It is concluded that neurons in NM project in a very discrete topographic, tonotopic and symmetrical fashion to NL on both sides of the brain, contributing to the binaural response properties and tonotopic organization of neurons in NL. The results also suggest that the organization of projections from NM to NL could provide a mechanism for the differential transmission delay required by a "place" model of low-frequency sound localization.

Animals↗

Comparative anatomy of melanin pigment in the stria vascularis. Evidence for a distinction between melanocytes and intermediate cells in the cat.

Although Corti in 1851 first described the presence of cochlear pigmentation in the stria vascularis (SV) of "very old" cats, modern studies have failed to find pigment consistently in the feline stria. While the variable presence of pigment in the feline SV would appear to contrast with this structure's uniform pigmentation in other mammalian species, variability in both the distribution and abundance of inner ear pigment has rarely been studied in any species. In the present study, the SV was examined light microscopically in sectioned material or whole-mounts from pigmented and albino animals of 5 species, including the cat, guinea pig, rabbit, ferret and mouse. In these species, the SV of each pigmented animal contained varying amounts of melanin pigment and none was found in the albino inner ear. Pigmented guinea pigs contained the most uniformly dense and least variable distribution of strial melanin, followed by the rabbit, mouse, ferret and cat. Several species also displayed more strial pigment apically and less basally. In cats, pigmented cells were principally located adjacent to the strial capillaries. Ultrastructural studies of the stria in pigmented cats revealed that these perivascular cells frequently contained an abundance of pigmented organelles and other structural features which allowed them to be distinguished from intermediate cells.

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