Biomedical subjects

B Mendelson

Publications and source records attributed to B Mendelson.

At least 19 recordsLinked to original sources

PubMed2000

The microanatomy of the distal arrector pili: possible role for alpha1beta1 and alpha5beta1 integrins in mediating cell-cell adhesion and anchorage to the extracellular matrix.

The arrector pili (AP) muscle is a small band of smooth muscle that attaches proximally to the bulge area of the pilosebaceous apparatus in the reticular dermis and extends up toward the epidermis. The distal anatomy of the AP and the anchorage mechanism allowing hair erection have not been previously described. Integrins are likely candidates mediating this attachment. Immunohistochemical techniques were used to determine the distribution of the following integrins: alpha1, alpha2, alpha3, alpha4, alpha5, alpha6 and beta1 as well as fibronectin. Frozen human scalp tissue was sectioned in traditional planes, obliquely and horizontally to visualize microanatomy in three dimensions. Histological examination revealed that the distal portions of smooth muscle fibers splay extensively between collagen bundles of the upper dermis. Integrin subunits alpha1, alpha5 and beta1 were expressed by the AP muscle. Analysis of the relative density of immunoreactivity in digitized sections revealed increased alpha5 subunit expression at the extracellular matrix (ECM)-muscle interface. These data suggest that anchorage of the AP muscle to the ECM is via alpha5beta1 integrin and alpha1beta1 integrin functions in muscle cell-cell adhesion. Extensive splaying of smooth muscle fibers may allow increased surface area contact between the ECM and smooth muscle cells expressing peripherally situated alpha5 integrin.

Aged↗

PubMed2000

Immunofluorescent microscopic investigation of the distal arrector pili: a demonstration of the spatial relationship between alpha5beta1 integrin and fibronectin.

Currently there is limited knowledge regarding the anatomy of the distal arrector pili (AP) muscle. A previous study implicated fibronectin and alpha5beta1 integrin binding as the anchor between the AP and the extracellular matrix (ECM). The purpose of this study was to strengthen this hypothesis. Serial frozen sections of human scalp skin were double-labeled via immunofluorescent staining for alpha5beta1 with fluorescein and fibronectin with rhodamine, followed by fluorescent microscopy. Granular staining for alpha5beta1 with fluorescein and smooth staining for fibronectin with rhodamine were seen at the periphery of the AP muscle bundles and along the distal fibers. Precise co-localization of alpha5beta1 and fibronectin was observed at the AP-ECM interface by means of a dual filter. Analysis of variance was used on the relative density of staining for each epitope. Staining for both epitopes was significantly brighter at the distal fibers than at the middle or proximal portions of the muscle. A computerized three-dimensional reconstruction provides a detailed picture of the microanatomy of the distal AP, which allows mathematical evaluation of the forces of contraction. The anatomic co-localization between alpha5beta1 and fibronectin strengthens our hypothesis that interaction of these epitopes mediates the attachment of the distal AP to the ECM.

Fibronectins↗

PubMed1997

Developmental changes in serotonergic receptor-mediated modulation of embryonic chick motoneurons in vitro.

Intracellular recordings were obtained from antidromically identified motoneurons in an embryonic chick spinal cord slice preparation at two developmental stages (embryonic days 12 and 18, E12 and E18) which bracket a critical period in spinal cord growth. The resting membrane potential of chick motoneurons did not change significantly between E12 and E18, but there was a significant decrease in neuronal input resistance. A small inward rectification was present in cells of both ages, although a lower proportion of E12 motoneurons exhibited inward rectification compared to E18 motoneurons. Injection of depolarizing current pulses revealed that most E12 motoneurons exhibited spike adaptation, while the majority of E18 motoneurons showed high frequency tonic firing. Bath application of serotonin (5-HT) and its agonists 5-carboxamido-tryptamine (5-CT, a 5-HT1 agonist) and alpha-methyl 5-HT (a 5-HT2 agonist) produced hyperpolarizing responses accompanied by decreased input resistance in all E12 motoneurons studied. The same three agonists produced depolarizing responses and increased input resistance in all E18 motoneurons studied. The effects of serotonergic agonists on motoneuronal excitability were tested using depolarizing current pulses. In most cases, serotonergic agonists caused a decrease in firing frequency during the hyperpolarizing response in E12 neurons. At E18, bath application of 5-HT, 5-CT or alpha-methyl 5-HT produced an increase in firing frequency in all motoneurons during the depolarizing response. Our results indicate that both 5-HT1 and 5-HT2 receptor subtypes contribute to modulation of chick motoneuron excitability and appear to reverse the polarity of their effects on membrane potential after a critical period in development of the spinal cord.

Analysis of Variance↗

PubMed1996

Overexpression of nerve growth factor in epidermis of transgenic mice preserves excess sensory neurons but does not alter the somatotopic organization of cutaneous nerve projections.

To determine how target-derived nerve growth factor (NGF) affects sensory neuronal survival and the development of topographic nerve projections in the spinal cord, anatomical studies were performed on transgenic mice that overexpress NGF in skin and other keratinized epithelial structures. Transgenic animals showed a 100% increase in the number of sensory neurons in specific dorsal root ganglia and exhibited significantly more fibers immunoreactive for calcitonin gene-related peptide in the dorsal horn compared to control animals. This confirms earlier studies which suggested that naturally occurring sensory neuronal death is decreased, or eliminated, in the transgenic mice. Nerve labeling studies showed that the somatotopic organization of cutaneous nerve projections was not altered in the transgenic animals. These data suggest that neuronal death does not act to remove sensory neurons that project to inappropriate regions of the spinal cord.

Animals↗

PubMed1996

Developmental changes in the effects of serotonin and N-methyl-D-aspartate on intrinsic membrane properties of embryonic chick motoneurons.

A spinal cord slice preparation was developed in order to study developmental changes in intrinsic membrane properties and in responses to N-methyl-D-aspartate and serotonin in embryonic chick motoneurons. Transverse spinal cord slices were obtained from chick embryos over a series of developmental stages (embryonic days 12-18). Intracellular recordings were obtained from 87 antidromically identified motoneurons. During the stages examined, the average resting membrane potential did not vary significantly, the voltage threshold of current-evoked action potentials became significantly more negative, there was a non-significant trend towards a decrease in the recorded input resistance, but there were no significant changes observed in the membrane time constant. There were significant developmental changes in the waveform of the current-evoked action potentials. The average amplitude of the action potentials increased over the stages studied, while the action potential duration measured at half-amplitude decreased. All of the motoneurons examined were maximally depolarized by bath application of 50 microM N-methyl-D-aspartate. The depolarization persisted in the presence of tetrodotoxin but was blocked by 100 microM 2-amino-5-phosphonopentanoic acid and, therefore, was at least partially due to a direct action of N-methyl-D-aspartate on motoneuronal receptors. The average amplitude of the N-methyl-D-aspartate-induced depolarizations decreased significantly over the stages examined. In contrast, bath application of 50 microM serotonin produced either depolarizing or hyperpolarizing responses depending on the developmental age of the motoneuron. Serotonin induced a depolarization in about 50% of the motoneurons at embryonic day 12, 69% of the motoneurons at embryonic day 15 and 100% of the motoneurons recorded from at embryonic day 18. These findings reveal important developmental changes in intrinsic membrane responses and action potential properties of chick motoneurons recorded from a slice preparation. We have also documented changes in the motoneuronal responses to serotonin, a neurotransmitter used by a major descending projection, and N-methyl-D-aspartate, which activates glutamate receptors known to contribute to synaptic activity in segmental circuits.

Action Potentials↗

PubMed1994

Chronic embryonic MK-801 exposure disrupts the somatotopic organization of cutaneous nerve projections in the chick spinal cord.

The effect of altering neural activity on the development of the central projections of cutaneous and muscle sensory neurons was studied in the embryonic chick spinal cord. Animals were treated chronically with MK-801, a non-competitive N-methyl-D-aspartate receptor antagonist, during the period when both cutaneous and muscle sensory afferents form connections in the spinal cord. Daily applications of MK-801 began on embryonic day 5, 1 day before sensory collaterals penetrate the spinal cord gray matter, and continued until the animals were analyzed (at embryonic day 14). The patterns of cutaneous and muscle sensory nerve projections were determined by applying fluorescent tracers to individual, identified peripheral nerves. MK-801 treatment did not overtly alter the pattern of muscle afferent projections. However, in the MK-801-treated embryos, the somatotopic organization of cutaneous afferent projections was dramatically altered. Normally, the projections formed by the lateral femoral cutaneous and the medial femoral cutaneous nerves are located immediately adjacent to one another in the lumbar dorsal horn, with little overlap. In the MK-801-treated embryos, the projections from these two cutaneous nerves both expanded significantly within dorsal horn laminae to become almost completely superimposed. These data suggest that MK-801 disrupts the development of the somatotopic organization of cutaneous afferent projections in the spinal cord.

Afferent Pathways↗

PubMed1994

Ontogeny and effect of activity on proenkephalin mRNA expression during development of the chick spinal cord.

Numerous studies have shown in the adult nervous system that mRNA expression can be regulated by neuronal activity. To examine the effect of activity during embryogenesis, the ontogeny of proenkephalin mRNA expression and expression following activity blockade was investigated during development of chick spinal cord. A cDNA fragment (ca. 0.5 kb) coding for chick proenkephalin was cloned and sequenced. With this cDNA, a cRNA probe was made to examine proenkephalin mRNA expression in the spinal cord during embryogenesis. Proenkephalin mRNA was expressed in spinal cord in clusters of cells located in the developing dorsal horn and intermediate lamina at the earliest stages examined (stage 22; E4). Proenkephalin-positive cells in the intermediate lamina were located immediately adjacent to the ventricular zone. At stage 28 (E6) an additional cluster of proenkephalin mRNA-positive cells was seen at the lateral border of the developing intermediate lamina. At stage 33 (E7.5-5-8) the pattern of hybridization positive cells was similar to earlier stages, but individual cells could be identified. At stage 39 (E13) densely labeled cells were seen throughout the dorsal horn and intermediate laminae including the column of Terni. To determine whether neural activity affects proenkephalin mRNA expression, d-tubocurarine (an inhibitor of neural activity) was injected into developing embryos. Following administration of d-tubocurarine a dramatic decrease was seen in proenkephalin mRNA hybridization in the dorsal horn and intermediate lamina of the spinal cord. This study demonstrates in vivo that changes in the level of neural activity can alter gene expression during embryogenesis and suggests that activity is required for expression of nervous system-specific genes.

Amino Acid Sequence↗

PubMed1992

Development of cutaneous and proprioceptive afferent projections in the chick spinal cord.

Muscle and cutaneous nerves were individually labeled with DiI in chick embryos to examine the development of sensory afferent arborizations in the spinal cord. Initially, cutaneous and muscle arbors were similar; both types first entered the spinal gray matter at stage 28-29 (embryonic day (E) 6). Differences in projections were first observed by late stage 34 (E8.5): muscle afferent collaterals extended almost unbranched to the level of motoneuronal dendrites while cutaneous afferents branched frequently and remained within the dorsal horn. Projections of putative small caliber axons into laminae 1 and 2, located laterally in the chick, did not develop until E13-14.

Afferent Pathways↗

PubMed1991

Specific monosynaptic sensory-motor connections form in the absence of patterned neural activity and motoneuronal cell death.

The importance of neural activity and motoneuronal cell death in the formation of specific synaptic connections between muscle afferents and motoneurons was studied in chick embryos. Patterned neural activity was blocked by applying d-tubocurarine (dtc) chronically to embryos during the period when sensory-motor connections are formed [stages (St) 28-42]. Dtc blocks neurogenic muscle contractions, thereby abolishing any temporal correlation between neural activity in motoneurons and stretch-sensitive afferents. The normal pattern of motoneuronal bursting is also blocked (Landmesser and Szente, 1986), as is motoneuronal cell death (Pittman and Oppenheim, 1979). Dtc applications were started more than 1 d before muscle sensory afferent collaterals make anatomical contact with motoneuronal dendrites and continued until St 38-42, when the pattern of synaptic connectivity was examined by recording synaptic potentials intracellularly from identified lumbosacral motoneurons upon stimulation of identified populations of muscle afferents. In both normal and dtc-treated animals, large monosynaptic excitatory potentials were evoked in homonymous motoneurons (those that supply the same muscle as the sensory afferents) and were often observed in motoneurons that supplied synergistic muscles. Monosynaptic potentials were uncommon in motoneurons supplying antagonistic muscles. The overt patterns of sensory-motor connections in normal and dtc-treated embryos were essentially identical. However, the amplitudes of the composite EPSPs recorded in dtc-treated animals were consistently about twice as large as normal. These observations suggest that neither normal patterns of neuronal activity nor motoneuronal cell death play a large role in determining the specificity of connections between the sensory and motor neurons involved in the stretch reflex.

Afferent Pathways↗

PubMed1990

Times of origin of brachial sensory neurons are not correlated with neuronal phenotype.

The times of origin (birthdays) of sensory and motor neurons that innervate the triceps brachii muscles of the bullfrog (Rana catesbeiana) were determined to learn whether neurons innervating a specific target are generated at a particular developmental time. 3H-thymidine (3H-TdR) was made available continuously throughout a specific developmental period. All neurons that innervated the triceps muscle in juvenile frogs (identified by filling cells retrogradely with HRP) were generated prior to metamorphosis. Triceps motoneurons were all postmitotic by early limb bud stage V. Triceps sensory neurons were generated over a protracted period of larval development, from stage V through early pre-metamorphic stage XV. Most large triceps sensory neurons were generated before the majority of the small cells. However, there was considerable overlap in the times of origin of the two populations; both large and small cells were generated at all stages of sensory neurogenesis. There was thus no strict relationship between sensory soma size and birthdate. Late-generated sensory neurons tended to be located in clusters within ganglia, whereas HRP-filled triceps neurons were not. These 3H-labeled clusters may represent clones of neurons which would indicate that late stage neuroblasts give rise to neurons that supply different peripheral targets. The time course of triceps neuronal generation paralleled that of all other brachial sensory neurons implying that the time of last cell division does not in itself determine either the target a neuron will innervate or the sensory modality to which it will respond.

Animals↗

PubMed1990

Specification of synaptic connections between sensory and motor neurons in the developing spinal cord.

Experimental studies of mechanisms underlying the specification of synaptic connections in the monosynaptic stretch reflex of frogs and chicks are described. Sensory neurons innervating the triceps brachii muscles of bullfrogs are born throughout the period of sensory neurogenesis and do not appear to be related clonally. Instead, the peripheral targets of these sensory neurons play a major role in determining their central connections with motoneurons. Developing thoracic sensory neurons made to project to novel targets in the forelimb project into the brachial spinal cord, which they normally never do. Moreover, these foreign sensory neurons make monosynaptic excitatory connections with the now functionally appropriate brachial motoneurons. Normal patterns of neuronal activity are not necessary for the formation of specific central connections. Neuromuscular blockade of developing chick embryos with curare during the period of synaptogenesis still results in the formation of correct sensory-motor connections. Competitive interactions among the afferent fibers also do not seem to be important in this process. When the number of sensory neurons projecting to the forelimb is drastically reduced during development, each afferent still makes central connections of the same strength and specificity as normal. These results are discussed with reference to the development of retinal ganglion cells and their projections to the brain. Although many aspects of the two systems are similar, patterned neural activity appears to play a much more important role in the development of the visual pathway than in the spinal reflex pathway described here.

Animals↗

PubMed1990

Specification of synaptic connections mediating the simple stretch reflex.

A variety of mechanisms underlie the specification of synaptic connections during development. In the monosynaptic stretch reflex in vertebrates, sensory neurones innervating muscle spindles are not determined until they make contact with a particular muscle. Instead, the muscle they supply appears to specify the pattern of central connections they establish with motoneurones. Developing thoracic sensory neurones made to project to novel peripheral targets in the forelimb of tadpoles project into the brachial spinal cord, something they never do in normal frogs. Moreover, these foreign sensory neurones make monosynaptic connections with the now functionally appropriate brachial motoneurones. Normal patterns of neuronal activity are not necessary for the formation of specific central connections. Neuromuscular blockade of developing chick embryos with curare during the period of synaptogenesis does not prevent the formation of correct sensory-motor connections. Competitive interactions among the afferent fibres also do not appear to be important in this process. When the number of sensory neurones projecting to the forelimb is drastically reduced during development, each afferent fibre still makes central connections of the same strength and specificity as normal. Together, these results suggest that peripheral targets induce some molecular change in developing sensory neurones such that they can recognize their appropriate synaptic partners in the spinal cord.

Animals↗

PubMed1989

Role of competition among sensory neurons in regulation of pattern of innervation at their central and peripheral targets.

1. The importance of competitive interactions among muscle sensory afferents on their projections to central and peripheral targets was studied by producing large reductions in the number of afferents during development. Removal of the brachial dorsal root ganglion (DRG2), which normally supplies the entire sensory innervation of the forelimb, in bullfrog (Rana catesbeiana) tadpoles caused a smaller number of neurons in the adjacent thoracic ganglion (DRG3) to sprout into the forelimb and into the brachial spinal cord. 2. Horseradish peroxidase labeling in postmetamorphic animals showed that DRG3 neurons innervating the triceps muscle arborize in a novel but now appropriate area of the spinal cord, the region containing motoneuronal dendrites. These foreign afferents do not arborize in inappropriate regions of the spinal gray matter, and their collaterals have the same rostrocaudal distribution as those of normal DRG2 muscle afferents. 3. After metamorphosis, the number of DRG3 sensory axons in individual triceps muscle nerves was determined. Normally, two-thirds of all triceps afferents project to the medial head alone, even though each of the three heads is of similar size and is contacted by similar numbers of motoneurons. After DRG2 removal, although the total number of DRG3 afferents projecting to the triceps muscle was smaller than normal, the medial head still received approximately two-thirds of the axons, just as in normal frogs. These results suggest that the proportional sensory innervation of the triceps muscle-heads is not dependent on competitive interactions among afferents. 4. DRG3 afferents projecting to the forelimb also sprouted to innervate appropriate brachial motoneurons. The average strength of connection between individual sensory and motor neurons was found to be the same as in normal animals, even though there was presumably more central target space available for each afferent axon. This suggests that the number and/or strength of central connections made by individual fibers may be an intrinsic property of muscle sensory neurons.

Animals↗

PubMed1986

Segmental homologies among reticulospinal neurons in the hindbrain of the zebrafish larva.

We have examined the morphology of identified reticulospinal neurons in larval zebrafish by retrogradely labeling them with horseradish peroxidase. We described the morphology of 27 different types of reticulospinal neurons found in the hindbrain 5 days after fertilization. Nineteen of these types are present as single identified neurons on each side of the brain; the others are present as pairs or small groups of cells. The hindbrain reticulospinal neurons are present in seven bilateral clusters that are spaced periodically along the neuraxis. Each cluster contains two to five different types of reticulospinal neurons. Cells with similar morphological features are found in adjacent clusters. By considering cell position within the cluster and axon pathway, nearly all of the cells can be assigned to one of about seven serially repeated classes. Independent morphological features of the cells support the same classification. We propose that the clusters represent hindbrain segments and that the neurons of the same class that are present in the different clusters are segmental homologues. Assuming that this series evolved by successive duplications and divergence of the primitive segments, we have analyzed the changes that may have occurred during the evolution of each new segment. Changes between ipsilaterally and contralaterally projecting axons may have occurred several times during the evolution of the series. In addition, cells may have been added or deleted.

Animals↗

PubMed1986

Development of reticulospinal neurons of the zebrafish. I. Time of origin.

The times of origin (birthdays) of identifiable types of reticulospinal (RS) neurons of the zebrafish (Brachydanio rerio) were determined in order to learn if differences in neuronal characteristics among cell types correlate with differences in their times of origin. The RS neurons are located in the midbrain and hindbrain and cell types can be identified by differences in their cell body sizes and positions, axonal projections, and dendritic arborizations (Metcalfe et al., J. Comp. Neurol. 251: 147-159, 1986). In this study, the birthdays of RS cells were determined by combining 3H-thymidine autoradiography with horseradish peroxidase histochemistry. The RS neurons that were examined were generated between 7 and 28 h after fertilization. Each cell type had a specific time of origin. Dorsally located neurons were always generated earlier than ventral neurons present at the same axial level. Often, but not always, larger and more lateral neurons were born earlier than smaller and more medial ones. There was no overall rostrocaudal gradient of neuronal generation and no overall correlation between time of origin and axonal pathway. However, the times at which RS neurons are generated may be important with respect to the establishment of their characteristic dorsoventral positions in the brain.

Age Factors↗

PubMed1986

Development of reticulospinal neurons of the zebrafish. II. Early axonal outgrowth and cell body position.

The sequence of axonal outgrowth and the early cell body positions of identifiable types of reticulospinal (RS) neurons of the zebrafish (Brachydanio rerio) were determined in order to learn if differences in neuronal characteristics among specific cell types correlate with differences in the times at which the cells develop. The time of axonal outgrowth and the location of the cells in the developing embryo were determined by filling RS neurons retrogradely with horseradish peroxidase from their growing axons over a series of developmental stages. Hindbrain cells developed in two distinct waves separated by about 10 hours. In the first wave, axons initiating growth at nearly the same time and from nearly the some location in the hindbrain diverged in their choice of an ipsilateral or contralateral pathway into the spinal cord. Individual types of RS neurons grew axons into the rostral spinal cord in a similar temporal sequence to that of their birthdays although the lag time between birthday and time of axonal outgrowth was variable (RS neuronal birthdays were reported in the previous paper, Mendelson: J. Comp. Neurol., 251:160-171 1986). All RS somata were initially observed along the ventral surface of the brain and were subsequently displaced dorsally. The displacement could be passive, due to growth of the ventral hindbrain, and could explain the previously observed dorsoventral differences in RS neuronal time of origin.

Age Factors↗

PubMed1986

Identified vertebrate neurons that differ in axonal projection develop together.

The development of identified reticulospinal neurons of the zebrafish (Brachydanio rerio) was studied in order to learn if cell specific differences in axonal projection are correlated with cell specific differences in time of neuronal development. We examined the development of individually known reticulospinal neurons that are located in close proximity in the hindbrain but that project axons to targets on opposite sides of the spinal cord. We observed that these identified neurons are generated together, and that their axons first arrive in the spinal cord together. We suggest that the selection of different axonal pathways by these neurons does not depend on the time that they develop.

Age Factors↗

PubMed1985

Soma position is correlated with time of development in three types of identified reticulospinal neurons.

The relationship among neuronal type, position, and time course of development of identified neurons was examined in the zebrafish (Brachydanio rerio). The cells studied, the reticulospinal neurons Mauthner, MiM1, and MiV1, are located within the same small region in the hindbrain, differ stereotypically in their positions within this region and also in their axonal projections. All of the cell types were generated and had initiated axonal outgrowth by the second day after fertilization. The time that these events occurred was specific for each cell type, with axonal outgrowth occurring about 10 hr after the neuronal birthday. Furthermore, the time of the events varied systematically according to the dorsoventral location of the neuron within the set.

Animals↗