Showing papers on "Nervous system published in 1986"

The structure of the nervous system of the nematode Caenorhabditis elegans

Abstract: The structure and connectivity of the nervous system of the nematode Caenorhabditis elegans has been deduced from reconstructions of electron micrographs of serial sections. The hermaphrodite nervous system has a total complement of 302 neurons, which are arranged in an essentially invariant structure. Neurons with similar morphologies and connectivities have been grouped together into classes; there are 118 such classes. Neurons have simple morphologies with few, if any, branches. Processes from neurons run in defined positions within bundles of parallel processes, synaptic connections being made en passant. Process bundles are arranged longitudinally and circumferentially and are often adjacent to ridges of hypodermis. Neurons are generally highly locally connected, making synaptic connections with many of their neighbours. Muscle cells have arms that run out to process bundles containing motoneuron axons. Here they receive their synaptic input in defined regions along the surface of the bundles, where motoneuron axons reside. Most of the morphologically identifiable synaptic connections in a typical animal are described. These consist of about 5000 chemical synapses, 2000 neuromuscular junctions and 600 gap junctions.

Expression of apolipoprotein E during nerve degeneration and regeneration

Abstract: A 37-kDa glycoprotein has been described recently, whose synthesis is dramatically increased after injury of the rat sciatic and optic nerves. Cells in the nerve sheath, distal to the site of injury, produce and secrete large amounts of this protein, so that by 3 weeks after injury, it represents 2-5% of the total soluble extracellular protein in the regenerating sciatic nerve sheath, although it fails to accumulate in damaged optic nerve. Results presented here reveal extensive homology between the 37-kDa nerve injury-induced protein and a well-studied serum protein, apolipoprotein E (apoE), that is involved in lipid and cholesterol metabolism and that has been shown recently to be present in adult and developing rat astroglia. Both proteins have identical isoelectric focusing points and similar molecular masses. Antibodies raised against the 37-kDa protein recognize apoE and anti-apoE serum crossreacts with the 37-kDa protein. Sequence data for two 14 amino acid stretches of the 37-kDa protein match identical regions of apoE. These data suggest that the 37-kDa protein is identical to serum apoE and that it could have similar functions to the latter. In the nervous system, for example, it may be involved in the mobilization and reutilization of lipid in the repair, growth, and maintenance of myelin and axonal membranes, both during development and after injury.

A protein induced during nerve growth (GAP-43) is a major component of growth-cone membranes.

Abstract: Growth cones are specialized structures that form the distal tips of growing axons. During both normal development of the nervous system and regeneration of injured nerves, growth cones are essential for elongation and guidance of growing axons. Developmental and regenerative axon growth is frequently accompanied by elevated synthesis of a protein designated GAP-43. GAP-43 has now been found to be a major component of growth-cone membranes in developing rat brains. Relative to total protein, GAP-43 is approximately 12 times as abundant in growth-cone membranes as in synaptic membranes from adult brains. Immunohistochemical localization of GAP-43 in frozen sections of developing brain indicates that the protein is specifically associated with neuropil areas containing growth cones and immature synaptic terminals. The results support the proposal that GAP-43 plays a role in axon growth.

Progress in Sensory Physiology

Abstract: 1 Introductory Remarks- 2 Plasticity in the Peripheral Somatosensory Nervous System- 21 Aspects of Plasticity in the Peripheral Nervous System- 22 Survival and Loss of Sensory Neurons After Lesions of the Peripheral Nervous System- 221 Effect of Crush or Transection of Peripheral Nerve on Neurons of Sensory Ganglia- 222 Trophic Dependence of Immature Sensory Neurons on the Periphery- 223 Effect of Peripheral Nerve Transection on Different Types of Sensory Neurons in Dorsal Root Ganglia- 224 Effect of Peripheral Nerve Section on Fibre Composition of Dorsal Roots- 225 Fate of the Lost neurons- 226 Sensory Cell Loss After Chemical Lesions of Afferent Fibres- 23 Collateral Sprouting of Primary Afferent Fibres in the Periphery- 231 Collateral Reinnervation of the Skin in Adult Mammals- 232 Collateral Sprouting in Neonates- 233 Effect of Neural Activity on Collateral Sprouting- 234 Collateral Sprouting of Trigeminal Afferents- 235 Collateral Sprouting and Sensory Recovery in Man- 236 Fate of Collateral Sprouts After Regeneration of Original Nerve- 24 Regeneration of Somatic Sensory Afferent Fibres- 241 Numbers of Axons in Nerves Regenerating After Crush or Transection- 242 Size of Regenerated Axons- 243 Effect of Denervation on Specialized Cutaneous Mechanoreceptors- 244 Reinnervation of Cutaneous Receptors by Regenerating Sensory Fibres- 25 Modality Specificity of Somatosensory Nerve Regeneration- 251 Regeneration of Myelinated Afferent Fibres to Hairy Skin- 252 Regeneration of Myelinated Afferent Fibres to Glabrous Skin- 253 Regeneration of Unmyelinated Afferent Fibres- 26 Major Conclusions- 3 Plasticity and the Mystacial Vibrissae of Rodents- 31 General Account of Pathway- 32 Normal Development of the Vibrissae and Their Neural Connections to the Cerebral Cortex- 33 Effects of Lesions and Manipulations in Prenatal, Neonatal and Developing Animals- 331 Damage of the Infraorbital Nerve- 332 Lesions to One or More Vibrissae- 333 The Effects of Supernumerary Vibrissae- 334 The Effects of Lesioning Unmyelinated Afferents- 335 Hyper- and Hypostimulation of Vibrissa Afferents- 336 Cortical Alterations- 34 Plasticity in the Vibrissa System of Adult Animals- 341 The SI Cortex- 342 The Ventral Posterior Medial Nucleus- 35 Major Conclusions- 4 Plasticity and the Spinal Dorsal Horn (with Notes on Homologous Regions of the Trigeminal Nuclei)- 41 Experimental Strategies for Demonstration of Plasticity in the Dorsal Horn of the Spinal Cord and Trigeminal Nuclei- 42 Overview of Dorsal Horn Organization- 421 Laminar Cytoarchitectonic Organization- 422 Laminar Organization of the Termination of Primary Afferent Fibres- 423 Microanatomical Organization of Low-Threshold Cutaneous Afferents- 424 Relation of Functional Properties to Lamination of the Dorsal Horn- 425 Inhibitory Receptive Fields- 43 Somatotopic Organization of the Dorsal Horn- 431 Dorsal Horn Neurons- 432 Somatotopy and Lamination- 433 Relation of Primary Afferent Projections to Dorsal Horn Somatotopy- 434 Relation Between Dorsal Horn Cell Dendritic Morphology and Receptive Field- 44 Effect of Lesions on Somatotopic Organization- 441 Dorsal Rhizotomy- 442 Chronic Spinal Lesions- 443 Peripheral Nerve Transection or Crush- 45 Mechanisms Underlying the Somatotopic Reorganization of Dorsal Horn Neurons- 451 Physiological and Pharmacological Evidence for the Existence of Normally Ineffective- Afferent Connections- 452 Spontaneous Changes of Receptive Fields- 453 Plasticity of Receptive Fields Induced by Afferent Activity- 454 Involvement of Unmyelinated Afferents in the Somatotopic Reorganization After Peripheral Nerve Injury- 455 Sprouting of Primary Afferent Fibres and Other Neurons as a Basis for Somatotopic Reorganization- 46 Plasticity of the Developing Dorsal Hor- 461 Development of Dorsal Horn Neurons and Primary Afferents- 462 Functional Plasticity in Development- 463 Somatotopic Reorganization Following Neonatal Peripheral Nerve Lesions- 464 Anatomical Plasticity of Neonatal Afferent Projections- 47 Major Conclusions- 5 Plasticity and the Dorsal Column Nuclei- 51 Advantages of the Dorsal Column Nuclei for Studies of Plasticity- 52 Organization of the Dorsal Column Nuclei- 521 Cytoarchitectonics- 522 Ascending Afferent Pathways- 523 Responses of Neurons to Natural Stimulation- 524 Core and Shell Organization- 525 Somatotopic Organization- 53 Alterations of Inputs to the Nuclei- 531 Section of Ascending Pathways- 532 Effects of Dorsal Rhizotomy- 533 Peripheral Nerve Section- 54 Evidence for Ineffective Afferent Connections- 541 Projections of Dorsal Roots and Peripheral Nerves- 542 Projections of Single Afferent Fibres- 543 Dendritic Spread of Cuneate Neurons- 544 Electrical Stimulation and Widefield Neurons- 545 Pharmacological Alterations of Receptive Fields- 55 Recovery from Sensorimotor Deficits Following Dorsal Column Lesions- 56 Plasticity of the DCN During Development- 561 Effects of Prenatal Lesions- 562 Effect of Neonatal Destruction of Unmyelinated Afferents- 57 Major Conclusions- 6 Plasticity and the Somatosensory Thalamus- 61 Experimental Strategies and Plasticity in the Ventral Posterior Nuclei of the Thalamus- 62 Anatomical Organization of Inputs and Outputs of the Ventral Posterior Nuclei- 621 Primate and Cat- 622 Raccoon- 623 Rat- 63 Responses of Neurons to Cutaneous Stimulation and the Effects of Anaesthetics and Other Drugs- 64 Somatotopic Organization of the VPL and VPM- 65 Effects of Alteration of Input on Somatotopic Organization- 651 Reversible Blockade of Afferents and the Immediate Expression of New Inputs- 652 Chronic Lesion of Afferent Pathways and Sprouting of Thalamic Afferents- 66 Major Conclusions- 7 Plasticity and the Somatosensory Cerebral Cortex- 71 Experimental Strategies and Cortical Plasticity- 72 Plasticity in the Cortex of Adult and Developing Primates- 721 Multiple Representations- 722 Thalamic Input and Intracortical Connectivity- 723 Responses of Cortical Neurons to Natural Stimulation- 724 Somatotopic Representation of the Hand in Areas 3b and 1- 725 Anatomy and Innervation of the Monkey Hand- 726 Anaesthetics and the Representation of the Hand- 727 Injury and Subsequent Regeneration of Peripheral Nerves- 728 Section and Ligation of Peripheral Nerves- 729 Effects of Repeated Stimulation on Cortical Representations- 7210 Cortical Damage- 73 Plasticity in the Cortex of Adult and Developing Cats- 731 Somatotopic Organization, Cytoarchitectonics and Neuronal Responses- 732 Thalamic Input and Ineffective Thalamocortical Connections- 733 Effects of Anaesthetics and Other Drugs- 734 Cordotomy and Section of Ascending Tracts- 735 Blockage of Primary Afferent Input in Specific Dorsal Roots- 736 Damage to Peripheral Nerves and Effects of Usage on Cortical Representation- 737 Cortical Damage- 74 Plasticity in the Cortex of Adult and Infant Raccoons- 741 Somatotopic Organization and Cytoarchitectonics- 742 Neuronal Responses in SI Cortex and the Effects of Anaesthetics- 743 Ineffective Afferent Connections- 744 Effects of Amputation on Cortical Somatotopy- 75 Plasticity in the Cortex of Adult and Developing Rodents- 751 Somatotopic Organization and Cytoarchitectonics- 752 Section and Ligation of Peripheral Nerves in the Adult- 753 Effects of Perinatal Nerve Section or Limb Amputation- 754 Pharmacological Mechanisms Underlying Somatotopic Reorganization- 755 Cortical Damage- 76 Major Conclusions- 8 Concluding Remarks- 81 Plasticity During Development- 811 Disruption of a Growing System and the Influence of the Periphery- 812 The Influence of Afferent Axons and the Target Tissue- 82 Evaluation of Experimentally Induced Plasticity in Adult Animals- 821 Plasticity in the Peripheral Nervous System- 822 Somatotopic Organization in Intact Animals as a Baseline for Assessing Altered Connections- 823 Somatotopic-Artifacts in Regions Deprived of Their Normal Input- 824 Plasticity and the Level of the Neuraxis- 83 The Case for Ineffective Connections- 831 Elucidation of Sub-Threshold Inputs- 832 Somatotopically Inappropriate Projections of Afferent Axons- 84 Spatial Extent of Immediate and Long-Term Changes in Somatotopic Organization- 841 Distance Limits of Somatotopic Reorganization- 842 Sprouting and Synaptogenesis in the Mature System- 843 Recovery of Function- 85 Normal Physiological Mechanisms and Plasticity- 851 Inhibitory Receptive Fields and Partial Deafferentation- 852 Neurotransmitters and Neural Systems That Regulate Sensory Input- 86 Role of Plasticity in the Mature Somatosensory System- References

Effects of insulin, insulin-like growth factor-II, and nerve growth factor on neurite formation and survival in cultured sympathetic and sensory neurons

Abstract: Insulin and the insulin-like growth factors (IGFs) may directly affect the development of the nervous system. NGF, IGF-II, and insulin's effects on neurite formation and neuronal survival were studied in peripheral ganglion cell cultures from chick embryos. Neurite outgrowth was enhanced in a dose-dependent manner by insulin and IGF-II in sympathetic cell cultures. The half-maximally effective concentration, ED50, was about 0.4-0.6 nM for both polypeptides, and concentrations as low as 10 pM were active. However, in sensory neurons the ED50 for neurite outgrowth was about 30 nM for insulin and 0.1 nM for IGF-II, suggesting that these factors may have selective effects in different neuronal tissues. Neither serum nor the presence of non-neuronal cells was required for the response in sympathetic neurons. The specific anti-NGF antiserum inhibited the neurite outgrowth response to NGF but not to insulin nor IGF-II. Insulin and IGF-II additionally supported survival of sensory and sympathetic neurons; however, insulin was not as efficacious as NGF. The combination of high concentrations of NGF and insulin was no better than NGF alone in supporting sympathetic cell survival, or neurite outgrowth. This indicates that insulin acts on the same, or a subpopulation, of NGF-responsive neurons. These results support the hypothesis that insulin and its homologs belong to a broad family of neuritogenic polypeptides.

Distribution of neuronal receptors for nerve growth factor in the rat

Abstract: To survey the distribution of neuronal receptors for NGF, sections of the rat brain, spinal cord, and peripheral ganglia were incubated in vitro with radioiodinated NGF and examined by autoradiography. NGF binds selectively with high affinity to most sympathetic neurons and many primary sensory neurons together with their intraspinal or intramedullary axons. In autoradiographs of the brain, labeled neuronal perikarya are seen in the basal forebrain, the caudate-putamen, the medulla oblongata, the ventral cochlear nucleus, and the dorsal nucleus of the lateral lemniscus. The distribution of neurons binding NGF resembles the distribution of cholinergic neurons in the forebrain, but these 2 systems overlap very little in the brain stem. In extracts of the brain or spinal cord enriched for plasma membranes, avid binding sites are regionally manifest with properties similar to those of fetal peripheral neurons. The localization of neurons expressing the high- affinity receptor for NGF defies simple correlation with neurotransmitter function or embryogenesis.

Retinal ganglion cells lose response to laminin with maturation

Abstract: The decisive role played by adhesive interactions between neuronal processes and the culture substrate in determining the form and extent of neurite outgrowth in vitro1,2 has greatly influenced ideas about the mechanisms of axonal growth and guidance in the vertebrate nervous system. These studies have also helped to identify adhesive molecules that might be involved in guiding axonal growth in vivo. One candidate molecule is laminin, a major gly-coprotein of basal laminae3 which has been shown to induce a wide variety of embryonic neurones to extend neurites in culture4–8. Moreover, laminin is found in large amounts in injured nerves that can successfully regenerate but is absent from nerves where regeneration fails9–11. However, it is unclear to what extent the mechanisms that regulate axonal regeneration also operate in the embryo when axon outgrowth is initiated. Here we have examined the substrate requirements for neurite outgrowth in vitro by chick embryo retinal ganglion cells, the only cells in the retina to send axons to the brain. We show that while retinal ganglion cells from embryonic day 6 (E6) chicks extend profuse neurites on laminin, those from Ell do not, although they retain the ability to extend neurites on astrocytes via a laminin-independent mechanism. This represents the first evidence that central nervous system neurones may undergo a change in their substrate requirements for neurite outgrowth as they mature.

Human T-cell lymphotropic virus type III infection of the central nervous system. A preliminary in situ analysis.

Abstract: Patients with the acquired immunodeficiency syndrome (AIDS) are subject to a spectrum of central nervous system (CNS) disorders. Recent evidence implicates the human T-cell lymphotropic virus type III (HTLV-III) in the pathogenesis of some of these illnesses, although the cells infected by the virus have yet to be identified. Using in situ hybridization, we examined brain tissue from two patients with AIDS encephalopathy for the presence of HTLV-III RNA. In both cases, viral RNA was detected and concentrated in, though not limited to, the white matter. The CNS cells most frequently infected included macrophages, pleomorphic microglia, and multinucleated giant cells. Less frequently, cells morphologically consistent with astrocytes, oligodendroglia, and rarely neurons were also infected. The findings strengthen the association of HTLV-III with the pathogenesis of AIDS encephalopathy. In situ hybridization can be applied to routinely prepared biopsy tissue in the diagnosis of HTLV-III infection of the CNS. ( JAMA 1986;256:2360-2364)

Nerve growth factor receptor molecules in rat brain.

Abstract: We have developed a method to immunoprecipitate rat nerve growth factor (NGF) receptor proteins and have applied the method to detect NGF receptor molecules in the rat brain. Crosslinking 125I-labeled NGF to either PC12 cells or cultured rat sympathetic neurons yielded two radiolabeled molecules (90 kDa and 220 kDa) that were immunoprecipitated by monoclonal antibody 192-IgG. Further, 192-IgG precipitated two radiolabeled proteins, with the expected sizes (80 kDa and 210 kDa) of noncrosslinked NGF receptor components, from among numerous surface-iodinated PC12 cell proteins. These results demonstrate the specific immunoprecipitation of NGF receptor molecules by 192-IgG. We applied the 125I-NGF crosslinking and 192-IgG-mediated immunoprecipitation procedures to plasma membrane preparations of the following areas of rat brain: medial septum, cerebellum, brainstem, hippocampus, cerebral cortex, thalamus, and olfactory bulb. NGF receptor molecules of the same molecular masses as the peripheral receptor components were consistently detected in all of these regions and in preparations from whole brains. Removal of the peripheral sympathetic innervation of the brain did not eliminate these NGF receptor proteins, indicating that the receptor is endogenous to central nervous system tissues. We also observed retrograde transport of 125I-labeled 192-IgG from the parietal cortex to the nucleus basalis and from the hippocampus to the nucleus of the diagonal band of Broca and the medial septal nucleus. These findings demonstrate the presence in brain of NGF receptor molecules indistinguishable from those of the peripheral nervous system.

Dynamic changes in the dendritic geometry of individual neurons visualized over periods of up to three months in the superior cervical ganglion of living mice

Abstract: We describe a means of visualizing the same neuron in the superior cervical ganglion of young adult mice over intervals of up to 3 months. The dendrites of these neurons change during this interval; some branches retract, others elongate, and still others appear to form de novo. Thus, neuronal dendrites in this part of the nervous system are subject to continual change beyond what is usually considered the developmental period. The remodeling of postsynaptic processes further implies that the synaptic connections made onto these cells undergo substantial rearrangement well into adulthood.

Expression of neurofilament subunits in neurons of the central and peripheral nervous system: an immunohistochemical study with monoclonal antibodies.

Abstract: The extent to which all neurofilament (NF) subunits (NF68, NF150, NF200) are expressed by different populations of mature CNS and PNS neurons is controversial. We addressed this issue in immunohistochemical studies of mature bovine tissues using monoclonal antibodies specific for each bovine NF subunit. All three NF subunits were detected in the perikarya and neurites of both CNS and PNS neurons; they were seen in nearly all PNS neuronal perikarya, and in all identifiable CNS and PNS axons. Most, but not all, CNS neuronal perikarya contained each of these NF antigens. CNS neurons devoid of immunodetectable NF antigens were generally small. The presence of low levels of NF antigens in neurons with scant perikaryal cytoplasm may account for the apparent absence of NF immunoreactivity in some classes of neurons, although other explanations, such as microheterogeneity among NF proteins, could account for this finding. NF antigens were also seen in some cells of the diffuse neuroendocrine system (adrenal chromaffin cells and cells of the pars distalis and pars intermedia), but not in other cell types. We suggest that the expression of all three NF subunits is a common feature of CNS and PNS neurons and their processes, and of some cells of the diffuse neuroendocrine system. These findings have implications for hypotheses concerning the structure and function of the intermediate filaments of neurons, and for hypotheses concerning neurodegenerative diseases involving NF proteins.

Differential distribution of cell adhesion molecules during histogenesis of the chick nervous system

Abstract: We have compared the expression of the neural cell adhesion molecule (N- CAM) and the neuron-glial cell adhesion molecule (Ng-CAM) during histogenesis of the chick nervous system. Data from immunohistochemistry and photometry were combined to construct maps of the overall distribution and dynamics of CAM appearance and disappearance. Each CAM appeared in a characteristic spatial and temporal pattern in various areas during cell movement, fiber outgrowth, tract formation, and myelination. N-CAM was more uniformly distributed than Ng-CAM and was present on all neural cell bodies and processes of the CNS and PNS. In the adult, the staining pattern of N- CAM remained similar to that in the embryo, although the staining intensity was diminished. During embryonic development, Ng-CAM was expressed on extending neurites and migrating neurons. The appearance Ng-CAM in the CNS was correlated particularly with times of cell migration in spinal cord and cerebellum, and in regions undergoing neurite extension, such as the developing white matter of the spinal cord, the optic nerve, and the medial longitudinal fasciculus. Cell bodies not undergoing migration were negative for Ng-CAM. In the adult CNS, Ng-CAM was markedly decreased in myelinated fiber tracts like the white matter of the spinal cord but persisted in unmyelinated regions such as the olfactory bulb. In contrast, in the PNS (for example, the dorsal root ganglion and sciatic nerve), Ng-CAM appeared early on both cell bodies and neurites, and it continued to be present on both in the adult, even in the presence of myelin. Maps comparing the relative distribution of Ng-CAM and N-CAM showed dynamic reversals as the nervous system developed and, as a result, the pattern of CAM expression was markedly different in embryos and adults. This difference appears to reflect changes in the roles of selective adhesion and of the two neuronal CAMs at different times of development.

Capsaicin induces a depletion of calcitonin gene-related peptide (CGRP)-immunoreactive nerves in the cardiovascular system of the guinea pig and rat.

Abstract: We have demonstrated that calcitonin gene-related peptide (CGRP) immunoreactivity is widely distributed in cardiac and perivascular nerves of the guinea pig and rat. In the guinea pig the number and distribution of CGRP-immunoreactive nerve fibres closely paralleled that of fibres containing substance P, the two immunoreactivities being found invariably to coexist in the same perivascular networks and terminals. In the rat, CGRP-immunoreactive cardiovascular nerves had a similar distribution to those containing substance P, but in contrast to the guinea pig the former were far more numerous. Marked regional variations were observed in the density of the CGRP-immunoreactive innervation in both species. The CGRP-immunoreactive content of tissue extracts was in close agreement with the immunocytochemical findings, the highest levels of CGRP occurring in the mesenteric artery (guinea pig and rat) and inferior vena cava (guinea pig). Following capsaicin treatment of adult guinea pigs and neonatal rats, there was a significant loss of CGRP-immunoreactive nerves in the two species. In the guinea pig, substance P-and CGRP-immunostained fibres were depleted to a similar extent, throughout the cardiovascular system. However, the loss of rat CGRP-immunoreactive nerves was dose-dependent and displayed considerable variation, some perivascular nerve networks appearing less susceptible than others to the action of capsaicin. The results suggest that there may be species differences in the sensitivity of CGRP-containing nerves to capsaicin treatment, but at least the majority of CGRP-immunoreactive cardiovascular nerves may be presumed to be sensory in origin.

Neuropeptide‐Fmrfamide‐Like immunoreactivity in drosophila: Development and distribution

Abstract: Neuropeptide-FMRFamide-like immunoreactivity was characterized in the fruit fly, Drosophila melanogaster In the adult central nervous system, a stereotypic pattern of immunoreactive cell bodies and immunoreactive nerve processes and varicosities was observed, indicating a neurochemical role for FMRFamide-like substance(s) in Drosophila Localization of immunoreactivity in the central nervous system of early larval stage revealed that the majority of the prominent FMRFamide-like immunoreactive neurons were already differentiated The FMRFamide-like immunoreactive neurons remain immunoreactive throughout postembryonic stage and persist in the adult central nervous system In the larva, in addition to the central nervous system, FMRFamide-like immunoreactivity was localized in the fibers innervating the ring gland, in the ganglion innervating the gut and in the gastric caeca

The appearance of an L1-like molecule in the chick primary visual pathway

Abstract: A monoclonal antibody, 8D9, has been obtained that binds to axons in the chick nervous system. Biochemical and immunological experiments indicate that the 8D9 antigen is related to the mouse L1 cell-adhesion molecule. The results of immunohistochemical experiments using monoclonal antibody 8D9 to study the development of the chick visual system are consistent with the 8D9 antigen functioning in axon fasciculation.

Effects of octopamine, dopamine, and serotonin on production of flight motor output by thoracic ganglia of Manduca sexta.

Abstract: Effects of biogenic amines on a centrally generated motor pattern in Manduca sexta were examined by pressure injecting nanomole to micromole amounts of octopamine, dopamine or serotonin into thoracic ganglia. Motor output was recorded extracellularly from a pair of antagonistic flight muscles and their motor neurons. The monoamines were found to alter production of a motor pattern that produces rhythmic wing flapping (10 Hz) and exhibits phase relationships similar to those in the flight pattern of intact moths. In mesothoracic ganglia with sensory nerves intact, octopamine (4 X 10(-9) mol) injected into lateral regions evoked regular firing of a single motor neuron, whereas a higher dose (4 X 10(-8) mol) often elicited the flight motor pattern. In the absence of sensory input, these doses of octopamine had little effect. Low doses (10(-10) mol) greatly enhanced motor responses to electrical stimulation of a wing sensory nerve. Dopamine (2 X 10(-10) mol) injected into the medial region of the mesothoracic ganglion elicited the flight motor pattern in the presence or absence of sensory input. Rhythmic output induced by dopamine (5 X 10(-10) mol) was suppressed by injecting serotonin (5 X 10(-10) mol) into the same region. These findings demonstrate that dopamine, octopamine, and serotonin have different effects on motor output in Manduca and suggest that these amines are involved in initiating, maintaining and terminating flight behavior, respectively. Octopamine may elicit flight production by enhancing the efficacy of sensory transmission thereby increasing excitability or arousal. Dopamine may act on interneurons involved in generating the flight motor pattern.

Distribution of stage-specific neurite-associated proteins in the developing murine nervous system recognized by a monoclonal antibody.

Abstract: A monoclonal antibody, 4D7, obtained with embryonic rat brain as an immunogen, recognizes an epitope on 3 protein species of 150–160, 100– 110, and 80 kDa, present in mouse and rat brain during the fetal period. Vital immunostaining of dissociated cultures of fetal forebrain indicates that the antigen is localized largely on the external plasma membrane of a subpopulation of neurites. Immunocytochemistry reveals that the distribution of the antigen in vivo is restricted to the nervous system. Immunoreactivity is concentrated primarily in the pathways of a limited set of CNS and PNS axon systems during early stages of their development, as delineated by staining with the neurofilament antibody, C2. Depending on the particular axon system, immunoreactivity with 4D7 persists only for one to several days of prenatal or perinatal development. In the spinal cord, stage-specific- neurite-associated proteins (SNAP) expression occurs first along motor axon pathways on embryonic day (E) 10 and then within the nerve trunks of dorsal root ganglia and the commissural fiber system on E11. Immunoreactivity is detectable among most cranial nerves starting in the interval from E11 to E13. Within the brain, the onset of SNAP expression within several discrete axon tracts occurs in the interval E14–16, including the lateral olfactory tract, anterior commissure, corpus callosum, fasciculus retroflexus, and fornix. Immunoreactivity within the embryonic intermediate zones of some structures matches the location of certain other axon systems. Sites of 4D7 staining which do not correspond to the location of axon populations include the internal portion of the external granular layer of the postnatal cerebellum and the cortex of the reeler mutant mouse. The predominant localization of the 4D7 antigen among axon systems and its precisely regulated spatio- temporal pattern of expression are consistent with the possibility that the SNAP antigens play a significant role in the early stages of growth of axonal tracts in vivo.

In situ hybridization histochemistry for the analysis of gene expression in the endocrine and central nervous system tissues: a 3-year experience.

Abstract: We report our experience in development of the in situ hybridization (ISH) procedure to detect messenger RNAs (mRNAs) coding for various molecules involved in endocrine glands and central nervous system activity, including mRNAs coding for endorphin precursors [preproenkephalin A (PPA), pro-opiocortin (POMC)], vasopressin, and transferrin. Various conditions of fixation and handling of the tissues were tested to establish optimal parameters for mRNA detection. Double-stranded DNA probes labeled by nick translation, synthetic oligonucleotides labeled at their 5' end, as well as single-stranded RNA probes were used, after incorporation of 32P- or 35S-labeled nucleotides. Specific requirements for efficient and reproducible ISH investigations are discussed. Cells expressing the PPA gene in the adrenal medulla and in the brain were detected by ISH. The results show that ISH is as sensitive as immunohistochemistry in detecting peptide-producing cells in the adrenal and that it allows detection of PPA cell bodies in brain in conditions in which they are inconstantly detected by immunohistochemistry. Unilateral destruction of substantia nigra provokes a dramatic decrease in the number of neurons expressing the PPA gene in the contralateral striatum. Cells expressing the POMC gene were detected in the pituitary of various species including man and in the rat arcuate nucleus. Neurons containing vasopressin mRNA were visualized in the supraoptic paraventricular and suprachiasmatic nucleus of the adult rat by using a synthetic oligonucleotide probe. Transferrin gene expression was shown in the central nervous system of the rat brain in two cell populations, the oligodendrocytes and the epithelial cells of the choroid plexus, by demonstration of simultaneous presence in them of transferrin immunoreactivity together with transferrin mRNA. These results show that the ISH procedure is a technique that can be routinely used to investigate gene transcription anatomically in complex heterocellular tissues such as the endocrine glands and the nervous system.

Relation of animal size to convergence, divergence, and neuronal number in peripheral sympathetic pathways.

Abstract: The enormous range of animal size raises a fundamental problem: How do larger animals maintain adequate control of peripheral structures that are many times more massive and extensive than the homologous structures in smaller animals? To explore this question, we have determined neuronal number, the number of axons that innervate each neuron (convergence) and the number of neurons innervated by each axon (divergence), in a peripheral sympathetic pathway of several mammals (mouse, hamster, rat, guinea pig, and rabbit). The average adult weights of these species vary over approximately a 65-fold range. However, the number of superior cervical ganglion cells increases by only a factor of 4 between the smallest of these animals (mice; about 25 gm) and the largest (rabbits; about 1700 gm); the number of spinal preganglionic neurons that innervate the ganglion increases by only a factor of 2. Thus, the number of nerve cells in the sympathetic system does not increase in proportion to animal size. On the other hand, our results indicate that there are systematic differences across these species in the number of axons that innervate each ganglion cell and in the number of ganglion cells innervated by each axon. We suggest that modulation of convergence and divergence in sympathetic ganglia allows this part of the nervous system to effectively activate homologous peripheral targets over a wide range of animal size.

Distribution of the adhesion molecules N-CAM and L1 on peripheral neurons and glia in adult rats

Abstract: There is considerable evidence that the cell surface glycoproteins N-CAM and L1 are important mediators of cell-cell adhesion in the nervous system, at least during development. Numerous studies have been devoted to the molecular properties of these proteins and their adhesion role in embryonic and early postnatal development. Much less is known about their importance in mature tissues. A rigorous and comprehensive description of the cell distribution of these molecules in the adult nervous system would clearly form a useful baseline for functional and biochemical studies. In the present work we have addressed this issue and studied the distribution of N-CAM and L1 throughout adult, as opposed to developing, rat peripheral nervous tissue. Particular attention was paid to the ganglia of the enteric nervous system, since adhesion mechanisms within these ganglia are likely to be placed under unusual demands. We report, for the first time, the presence of N-CAM and L1 on mature sensory, sympathetic and enteric neurons in adult rats. Thus, immunostaining of cell suspensions or short-term cultures showed N-CAM and L1 surface labelling on sympathetic and both large and small dorsal root sensory neurons. Both antigens were also present on the surface of enteric neurons in cultures prepared from 10-day-old rats and neonatal guinea pigs. Immunostaining of sections of enteric ganglia from adults indicated that both molecules were also expressed by mature enteric neurons. In sections of mature sciatic nerve neither N-CAM nor L1 immunoreactivity were detected at the site where the plasma membrane of myelinated axons meets the ad-axonal plasma membrane of the myelin-forming Schwann cell. Thus, both N-CAM and L1 were detected on all major classes of peripheral neurons, while their levels in the plasma membrane of myelinated axons may be significantly down-regulated. Similarly, both N-CAM and L1 were present on all major classes of non-myelin-forming peripheral glia in adult rats. This includes the enteric glial cells of the myenteric ganglia, non-myelin-forming Schwann cells in the sciatic nerve, sympathetic trunk and fine autonomie nerves in the gut wall, and the satellite glial cells of sympathetic and dorsal root sensory ganglia. In contrast, myelin-forming Schwann cells did not express detectable levels of N-CAM and only very low levels of L1, which was mainly located near the nodes of Ranvier. On the basis of these findings the prediction would be that, with the exception of myelinated fibres, N-CAM and L1 operate in parallel to link neurons and glia throughout the adult rat PNS. It remains to be seen whether myenteric ganglia, a part of the nervous system exposed to an unusual degree of mechanical stress, possess additional adhesive mechanisms. Myelin-forming Schwann cells appear to differ from other peripheral glia in their adhesive interactions with neuronal membranes since they do not express detectable levels of N-CAM and and show only low levels of L1.