Biomedical subjects

C E Carr

Publications and source records attributed to C E Carr.

At least 19 recordsLinked to original sources

PubMed2001

Expression of the Kv3.1 potassium channel in the avian auditory brainstem.

The Shaw-like potassium channel Kv3.1, a delayed rectifier with a high threshold of activation, is expressed in the time coding nuclei of the bird auditory brainstem. In both barn owls and chickens, Kv3.1 mRNA was expressed in the cochlear nucleus magnocellularis (NM) and the nucleus laminaris (NL). Western blot analysis showed that an antibody raised against the synthetic peptide sequence of rat Kv3.1 (rKv3.1) specifically recognized the same 92 kDa protein bands in both rat and chicken synaptosomal preparations. Immunohistochemical analyses using this anti-rKv3.1 antibody revealed a prominent gradient in Kv3.1 immunoreactivity along the tonotopic axis of the barn owl NM and NL and a less prominent gradient in the chicken. The precise localization of the Kv3.1 immunoproduct was resolved by electron microscopy. In both the owl and the chicken, Kv3.1 was targeted postsynaptically in NM and NL. The major difference in localization of Kv3.1 protein between the two birds was the expression of Kv3.1 in the NM axons and terminals in the region of the barn owl NL. This location of Kv3.1 channels supports its postulated function in reducing the width of action potentials as they invade the presynaptic terminal. The presynaptic localization may be a specialization for enabling neurons in owl NM to transmit high-frequency temporal information with little jitter.

Alternative Splicing↗

PubMed2001

The cytoarchitecture of the nucleus angularis of the barn owl (Tyto alba).

The cochlear nucleus angularis (NA) of the barn owl (Tyto alba) was analyzed using Golgi, Nissl, and tract tracing techniques. NA forms a column of cells in the dorsolateral brainstem that partly overlaps with, and is rostral and lateral to, the cochlear nucleus magnocellularis (NM). Highest best frequencies are mapped in lateral NA (NAl), intermediate in medial NA (NAm), and lowest in the foot region (NAf). Cell density followed the tonotopic axis and decreased with decreasing best frequency. NA contained four major cell classes: planar, radiate, vertical, and stubby. Planar and radiate classes were further subdivided into bipolar and multipolar types according to their number of primary dendrites. Planar neurons were confined to an isofrequency band, whereas radiate neurons had dendrites that could extend across an isofrequency band. Vertical cells had long dendrites oriented perpendicularly to isofrequency bands. Stubby cells were the most numerous and were confined to an isofrequency band because of their short dendrites. Neurons in each of these four classes projected to the inferior colliculus and dorsal nucleus of the lateral lemniscus.

Animals↗

PubMed2001

Tonotopic and somatotopic representation in the nucleus basalis of the barn owl, Tyto alba.

We have investigated the somatosensory and auditory representations in the nucleus basalis of the barn owl. In pigeons and finches, the nucleus basalis contains a representation of the beak and an auditory area. In the barn owl, the nucleus basalis also contains a complete somatotopic map of the head and body (as in the budgerigar), with a tonotopically organized auditory area in close proximity to the representation of the facial ruff and the preaural area. Recordings within and around the nucleus basalis revealed predominantly (about 80%) contralateral responses to somatic stimulation. The somatotopic map was oriented with the head down and rostral. Penetrations revealed an over-representation of the feet in dorsal basalis, followed by the rest of the body and wings more ventrally. Towards more rostral positions in nucleus basalis, responses from the head and beak predominated ventrally. The auditory response area was encountered below the region that responded to stimulation of the facial ruff and preaural flap regions and above a region responsive to beak stimulation. Auditory responses were tonotopically organized, with low best frequencies dorsal. Some penetrations yielded predominantly monaural responses with a fairly broad dynamic range, similar to those recorded from the ventral nucleus of the lateral lemniscus (LLV) and the cochlear nucleus angularis, whereas other penetrations contained predominantly binaural responses sensitive to interaural time differences (ITD). The physiological responses could be predicted on the basis of auditory projections to the nucleus basalis. An injection of biotinylated dextran amine (BDA) in the auditory region of nucleus basalis retrogradely labeled cells in both the caudal and rostral parts of the intermediate lateral lemniscal nucleus (LLIc and LLIr), and a few cells in the anterior part of the dorsal lateral lemniscal nucleus (LLDa, previously known as nucleus ventralis lemnisci lateralis, pars anterior, or VLVa) and in the posterior part of the dorsal lateral lemniscal nucleus (LLDp, previously known as nucleus ventralis lemnisci lateralis, pars posterior, or VLVp). A large injection of cholera toxin B-chain (CTB) into the nucleus basalis also produced dense retrograde labeling of a previously unidentified nucleus on the lateral aspect of the rostral pons, that we here call nucleus pontis externus (PE). An injection of CTB into PE produced dense retrograde labeling of the contralateral dorsal column nuclei and anterograde labeling of the ipsilateral lateral and dorsolateral nucleus basalis. Together these results define major somatosensory and auditory projections to the owl telencephalon that bypass the thalamus.

Afferent Pathways↗

PubMed2000

Development of the auditory brainstem of birds: comparison between barn owls and chickens.

Birds have proved to be extremely useful models for the study of hearing function. In particular, chickens and barn owls have been widely used by a number of researchers to study diverse aspects of auditory function. These studies have benefited from the advantages offered by each of these two species, including differences of auditory specialization. Direct comparisons between chickens and barn owls become complicated when the degree of auditory specialization and their modes of development are brought into consideration. In this article we review the available literature on the development of the auditory brainstem of chickens and barn owls in the context of such differences. In addition, we present a time line constructed on the basis of common stages of structural differentiation, rather than chronological time. We suggest that such a time line should be considered when discussing comparative data between these two species. Such an approach should facilitate the interpretation of similarities and differences observed in the developmental processes of the auditory system of chickens and barn owls.

Animals↗

PubMed1999

Development of calretinin immunoreactivity in the brainstem auditory nuclei of the barn owl (Tyto alba).

The early development of calretinin immunoreactivity (CR-IR) was described in the auditory nuclei of the brainstem of the barn owl. CR-IR was first observed in the auditory hindbrain at embryonic day (E17) and a day later (E18) in the inferior colliculus. In each of the auditory nuclei studied, CR-IR did not develop homogeneously, but began in the regions that map high best frequencies in the adult barn owl. In the hindbrain, CR-IR was first observed in the rostromedial regions of the cochlear nucleus magnocellularis and the nucleus laminaris, and in the dorsal regions of the nucleus angularis and in the nucleus of the lateral lemniscus. In the inferior colliculus, CR-IR began in the ventral region of the central core. The edge of these gradients moved along the future tonotopic axes during the development of all nuclei studied, until adult patterns of CR-IR were achieved about a week after hatching.

Animals↗

PubMed1999

Evolution of time coding systems.

The auditory and electrosensory systems contain circuits that are specialized for the encoding and processing of microsecond time differences. Analysis of these circuits in two specialists, weakly electric fish and barn owls, has uncovered common design principles and illuminated some aspects of their evolution.

Algorithms↗

PubMed1999

Transforming growth factor beta from multiple myeloma cells inhibits proliferation and IL-2 responsiveness in T lymphocytes.

Multiple myeloma (MM) is a cancer of plasma cells, characterized by profound suppression of host immune responses. Here we show that MM cell lines significantly suppress the proliferation, blasting, response to interleukin-2 (IL-2), and expression of CD25 by concanavalin A (Con A)-activated or allostimulated peripheral blood T lymphocytes. T cells arrest in the G1 stage of the cell cycle, and do not enter the IL-2 autocrine growth pathway. T cell inhibition was mediated by a soluble factor. MM cell lines did not produce IL-10 but did produce large amounts of transforming growth factor beta1 (TGF-beta1). T cells were assessed for their ability to respond to IL-2 when co-cultured with MM cells in the presence or absence of the TGF-beta inhibitor, TGF-beta latency-associated peptide (LAP). MM cells suppressed IL-2 responses but this inhibition was completely reversed by TGF-beta LAP. A CD25-, IL-2-dependent blast cell line was not inhibited by MM cells or rhTGF-beta, confirming the specificity of the inhibition mechanism for the IL-2 autocrine growth pathway. We conclude that MM cells suppress T cells in their entry into the autocrine IL-2/CD25 pathway and in response to IL-2, and that TGF-beta has a significant role to play.

Adjuvants, Immunologic↗

PubMed1999

A morphological study of the cochlear nuclei of the pigeon (Columba livia).

The pigeon cochlear nucleus angularis (NA) and nucleus magnocellularis (NM) were analyzed with Golgi and Nissl techniques. NA was divided into a medial NAm and NA proper, which could be subdivided further into an intermediate NAi and lateral NAl. NAm contained a mostly homogeneous population of a unique multipolar cell type with very short dendrites and large somatic spines. NA proper contained four cell types: large, medium, and small multipolars, and medium bipolar. The medium multipolar cells were most common, and resembled the multipolar cells of the mammalian ventral cochlear nucleus. NM presented a homogenous appearance with a mediolateral gradient of cell size and shape. Medially located higher best frequency NM principal cells had round cell bodies with small somatic spines and few dendrites. By comparison, laterally located low best frequency NM stellate cells had more dendrites and spindle shaped cell bodies. The similarities between the cell types of NA and the cell types in the cochlear nuclei of other amniote vertebrates may be due to homology or convergent evolution.

Animals↗

PubMed1999

A clinical trial of radioimmunotherapy with 67Cu-2IT-BAT-Lym-1 for non-Hodgkin's lymphoma.

UNLABELLED: Encouraged by the results of 131I-Lym-1 therapy trials for patients with B-cell non-Hodgkin's lymphoma (NHL), this phase I/II clinical trial of 67Cu-2IT-BAT-Lym-1 was conducted in an effort to further improve the therapeutic index of Lym-1-based radioimmunotherapy. Lym-1 is a mouse monoclonal antibody that preferentially targets malignant lymphocytes. 67Cu has beta emissions comparable to those of 131I but has gamma emissions more favorable for imaging. The macrocyclic chelating agent 1,4,7,11-tetraazacyclotetradecane-N,N',N",N"'-tetraacetic acid binds 67Cu tightly to form a stable radioimmunoconjugate in vivo. METHODS: All 12 patients had stage III or IV NHL that had not responded to standard therapy; 11 had intermediate- or high-grade NHL. At 4-wk intervals, patients received up to four doses of 67Cu-2IT-BAT-Lym-1, 0.93 or 1.85-2.22 GBq/m2 (25 or 50-60 mCi/m2), with the lower dose used when NHL was detected in the bone marrow. RESULTS: 67Cu-2IT-BAT-Lym-1 provided good imaging of NHL and favorable radiation dosimetry. The mean radiation ratios of tumor to body and tumor to marrow were 28:1 and 15:1, respectively. Tumor-to-lung, -kidney and -liver radiation dose ratios were 7.4:1, 5.3:1 and 2.6: 1, respectively. This 67Cu-2IT-BAT-Lym-1 trial for patients with chemotherapy-resistant NHL had a response rate of 58% (7/12). No significant nonhematologic toxicity was observed. Hematologic toxicity, especially thrombocytopenia, was dose limiting. CONCLUSION: 67Cu remains an option for future clinical trials. This study established 67Cu-2IT-BAT-Lym-1 as a safe, effective treatment for patients with NHL.

Bone Marrow↗

PubMed1998

The role of dendrites in auditory coincidence detection.

Coincidence-detector neurons in the auditory brainstem of mammals and birds use interaural time differences to localize sounds. Each neuron receives many narrow-band inputs from both ears and compares the time of arrival of the inputs with an accuracy of 10-100 micros. Neurons that receive low-frequency auditory inputs (up to about 2 kHz) have bipolar dendrites, and each dendrite receives inputs from only one ear. Using a simple model that mimics the essence of the known electrophysiology and geometry of these cells, we show here that dendrites improve the coincidence-detection properties of the cells. The biophysical mechanism for this improvement is based on the nonlinear summation of excitatory inputs in each of the dendrites and the use of each dendrite as a current sink for inputs to the other dendrite. This is a rare case in which the contribution of dendrites to the known computation of a neuron may be understood. Our results show that, in these neurons, the cell morphology and the spatial distribution of the inputs enrich the computational power of these neurons beyond that expected from 'point neurons' (model neurons lacking dendrites).

Action Potentials↗

PubMed1998

Development of AMPA-selective glutamate receptors in the auditory brainstem of the barn owl.

AMPA receptor specific antibodies were used to study the distribution and development of glutamate receptor subtypes (GluR1-4) in nucleus magnocellularis, angularis, laminaris, and the superior olive of the barn owl. Each nucleus in the adult barn owl expresses characteristic levels of AMPA receptor subtypes, and all are enriched in the subunits associated with rapid desensitization (GluR2 and 4). In the auditory hindbrain of the barn owl, the levels of expression of all AMPA receptors were very low at the time of hatching. In all nuclei, the level of GluR1 immunoreactivity was low to undetectable at all ages studied. In the cochlear nuclei, angularis and magnocellularis, levels of GluR2/3 and GluR4 immunoreactivity increased over the first 2 weeks after hatching, coinciding with the morphological maturation of auditory nerve terminals in NM. In the nucleus laminaris and in the superior olive, GluR2/3 and GluR4 immunoreactivity reached adult-like patterns by 3 weeks after hatching. Thus, adult-like patterns of immunoreactivity appeared at least 1 month before the end of the sensitive period in all nuclei studied.

Animals↗

PubMed1997

Localization of AMPA-selective glutamate receptors in the auditory brainstem of the barn owl.

AMPA receptor subunit-specific antibodies were used to determine if the distribution of excitatory amino acid receptors in the owl's auditory brainstem and midbrain nuclei reflected specializations for temporal processing. Each auditory nucleus displays characteristic levels of immunostaining for the AMPA receptor subunits GluR1-4, with high levels of the subtypes which exhibit rapid desensitization (GluR4 and 2/3). In the auditory brainstem, levels of GluR2/3 and GluR4 were very high in the cochlear nucleus magnocellularis and the nucleus laminaris. The different cell types of the cochlear nucleus angularis and the superior olive were characterized by heterogeneous GluR2/3 and 4 immunostaining. GluR1 levels were very low or undetectable. In the lemniscal nuclei, most neurons contained low levels of GluR1, and dense GluR2/3 and GluR4 immunoreactivity, with high levels of GluR4 in the dendrites. Levels of GluR4 were higher in the anterior portion of the ventral nucleus of the lateral lemniscus. The divisions of the inferior colliculus could be distinguished on the basis of GluR1-4 immunoreactivity, with high levels of GluR4 and moderate levels of GluR1 in the external nucleus. No major differences were observed between the pathways for encoding time and sound level cues.

Animals↗

PubMed1997

Low-frequency pathway in the barn owl's auditory brainstem.

The cytology of the nucleus magnocellularis and the nucleus laminaris in the barn owl, as well as the axonal pathways connecting them, were studied. The interest was focussed on those regions of both nuclei coding the low-frequency end of the tonotopic spectrum (below approximately 2 kHz) because many previous reports on a variety of bird species had indicated significant differences to higher frequencies, both in morphology and physiology. Standard light- and electron microscopy, as well as immunocytochemistry and tract-tracing techniques, were used. The nucleus magnocellularis contains a distinct stellate cell type in the low-frequency region, in addition to neurons classified as a small version of the principal cell. In the nucleus laminaris, two cell types were characterized as distinct to the low-frequency region: stellate neurons with long, smooth dendrites, and multipolar neurons with thick, spiny dendrites. The low-frequency projections from the nucleus magnocellularis showed two terminal fields in the nucleus laminaris: one containing a rough tonotopic representation and a second one where all low-frequency projections converged. In addition, the anatomical basis for delay lines, which are known to play an important role in the coding of interaural time differences at higher frequencies, was not observed. The morphological differences observed at low frequencies in both nuclei, compared to the well-studied higher-frequency regions, may reflect inherent limitations to the accuracy in the processing of interaural phase disparities at low frequencies.

Animals↗

PubMed1996

Development of the time coding pathways in the auditory brainstem of the barn owl.

The barn owl's head grows after hatching, causing interaural distances to more than double in the first 3 weeks posthatch. These changes expose the bird to a constantly increasing range of interaural time cues. We have used Golgi and ultrastructural techniques to analyze the development of the connections and cell types of the nucleus magnocellularis (NM) and the nucleus laminaris (NL) with reference to the growth of the head. The time coding circuit is formed but immature at the time of hatching. In the month posthatch, the auditory nerve projection to the NM matures, and appears adult-like by posthatch day (P)21. NM neurons show a late growth of permanent dendrites starting at P6. Over the first month, these dendrites change in length and number, depending upon rostrocaudal position, to establish the adult pattern in which high best frequency neurons have few or no dendrites. These changes are not complete by P21, when NM neurons still have more dendrites than in the adult owl. The neurons of NL have many short dendrites before hatching. Their number is greatly reduced by P6, and then does not change during later development. Like NM neurons, NL neurons and dendrites grow in the first month posthatch, and at P21, NL dendrites are longer than those in the adult owl. Thus, the auditory brainstem circuits grow in the first month after hatching, but are not yet mature at the time the head reaches its adult size.

Animals↗

PubMed1996

Chick cochlear efferent neurons are not immunoreactive for calcitonin gene-related peptide.

The fluorescent retrograde tracer, rhodamine dextran amine, was unilaterally injected into the cochlear duct of anesthetized chicks. Retrogradely labeled cells were found bilaterally in the brainstem ventromedial to the superior olivary nucleus and to the ventral facial nucleus, and in the caudal pontine reticular formation between the dorsal facial nucleus and the abducens nerve root. Tissue sections containing retrogradely labeled cells were incubated in an antiserum to calcitonin gene-related peptide (CGRP) and a fluorescently labeled secondary antiserum. No double-labeled neurons were found, suggesting that chick cochlear efferent neurons do not contain CGRP or that levels of CGRP in these cells may be too low to be detected immunohistochemically.

Animals↗

PubMed1995

Enkephalin-like immunoreactivity in the chick brainstem: possible relation to the cochlear efferent system.

Mammalian lateral olivocochlear (LOC) neurons that are immunoreactive for choline acetyltransferase (ChAT) are also immunoreactive for enkephalin (Enk). To determine whether cochlear efferent neurons in birds might also contain Enk-like immunoreactivity (Enk-LI), we studied the auditory brainstem of the domestic chicken using antisera to ChAT, leucine-enkephalin (L-Enk) and methionine-enkephalin (M-Enk). Enk-LI terminals are found around, but not within, the superior olivary nucleus (SO) and the nucleus of the lateral lemniscus, pars intermedia (LLi). A moderate concentration of Enk-LI terminals is found ventromedial to the ventral facial nucleus (VIIv) where the ventrolateral group of ChAT-I cochlear efferent neurons is located. After colchicine injections into the lateral ventricle, a population of intensely stained Enk-LI perikarya was found in the nucleus of the lateral lemniscus, pars ventralis (LLv) with scattered cells in the LLi and the nucleus subceruleus ventralis (SCv). The distribution of Enk-LI and ChAT-I somata, however, never overlapped, even in adjacent sections. Thus, in the chick, Enk-LI perikarya are not distributed in areas where cochlear efferent neurons are found. Instead, a dense concentration of Enk-I terminals can be found in areas containing ChAT-I cochlear efferent neurons. The source of these enkephalinergic terminals may be a population of Enk-LI cells in the LLv.

Animals↗

PubMed1994

Choline acetyltransferase-immunoreactive cochlear efferent neurons in the chick auditory brainstem.

Cholinergic neurons in the chick auditory brainstem were studied with the aid of an antiserum to choline acetyltransferase (ChAT), the biosynthetic enzyme for acetylcholine. ChAT-immunoreactive (ChAT-I) neurons were found in a ventrolateral and a dorsomedial cell group. The ventrolateral group is a rostrocaudally directed column of cells that surround the superior olive (SO), are ventromedial to the ventral facial nucleus (VIIv), and are lateral to the nucleus pontis lateralis (PL) as far rostrally as the nucleus subceruleus ventralis. Cells in the dorsomedial group were found in the pontine reticular formation medial to the dorsal facial nucleus and lateral to the abducens nerve root. Occasionally, small ChAT-I cells were found in the crossed dorsal cochlear tract and in the medial vestibular nucleus near the dorsal border of the caudal nucleus magnocellularis (NM). No ChAT-I neurons or fibers were observed in NM, nucleus angularis, nucleus laminaris, in the nuclei of the lateral lemniscus, or in the nucleus mesencephalicus lateralis pars dorsalis. To determine which cholinergic neurons project to the cochlea, a double-labeling technique was used combining ChAT-I and the retrograde transport of biotinylated dextran amine (BDA) from the inner ear. Double-labeled cells were found bilaterally in both the ventrolateral and dorsomedial cell groups, with the exception of large ChAT-I cells dorsal to the SO, which do not appear to project to the cochlea. Cholinergic cells that project to the cochlea were classified into three morphological groups: multipolar, elongate, and round-to-oval. Both the ventrolateral and the dorsomedial cell groups appear to have a mixture of these different cell types. The average somal area of cholinergic cochlear efferents was 246 microns 2. Only about 70% of the cochlear efferent neurons, however, are cholinergic.

Animals↗

PubMed1993

An axon with a myelinated initial segment in the bird auditory system.

In the bird auditory brainstem, nucleus laminaris neurons compute interaural time differences by comparing inputs from two ears. Laminaris neurons in barn owls have short dendrites and axons with myelinated initial segments. We examined laminaris cells in chickens with a range of dendritic lengths to determine if neurons with long dendrites had normal axons. Neurons with short dendrites had myelinated initial segments while neurons with long dendrites had normal initial segments. Thus, the myelinated initial segment may serve to move the spike-initiation zone away from the somatodendritic compartment that integrates inputs from the two ears.

Animals↗