Showing papers on "Nervous system published in 1994"
TL;DR: It is now apparent that regulation of neuronal function by the recently identified members of the neurotrophin family is far more complex than envisioned on the basis of work with NGF, particularly for neurons in the central nervous system (CNS).
1,448 citations
TL;DR: Transgenic mice are generated in which neurons overexpress the human BCL-2 protein under the control of the neuron-specific enolase (NSE) or phosphoglycerate kinase (PGK) promoters to gain insight into the possible role of bcl-2 during NOCD in vivo.
1,093 citations
TL;DR: It is shown that mutant mice lacking BDNF have severe deficiencies in coordination and balance, associated with excessive degeneration in several sensory ganglia including the vestibular ganglion, and that BDNF is required for the survival and target innervation of particular neuronal populations.
Abstract: DURING vertebrate development, neuronal survival depends on target-derived neurotrophic factors1,2. Brain-derived neurotrophic factor3 (BDNF), a member of the neurotrophin family, can prevent the death of particular peripheral sensory neurons in vitro4–6, and of central motor neurons as well as dopaminergic and cholinergic neurons of the basal forebrain during development7–9. It also prevents the death of motor neurons and midbrain dopaminergic neurons induced by lesions8,10–12. Here we show that mutant mice lacking BDNF have severe deficiencies in coordination and balance, associated with excessive degeneration in several sensory ganglia including the vestibular ganglion. The few remaining vestibular axons fail to contact the vestibular sensory epithelia, and terminate in the adjacent connective tissue. Survival of sympathetic, midbrain dopaminergic and motor neurons is not affected. These results indicate that BDNF is required for the survival and target innervation of particular neuronal populations.
1,072 citations
TL;DR: The BDNF mutant homozygotes have substantially reduced numbers of cranial and spinal sensory neurons and expression of neuropeptide Y and calcium-binding proteins is altered in many neurons, suggesting they do not function normally.
1,049 citations
TL;DR: Astrocytes are shown to directly modulate the free cytosolic calcium, and hence transmission characteristics, of neighboring neurons, which suggests that the astrocytic-neuronal signaling is mediated through intercellular connections rather than synaptically.
Abstract: Although astrocytes have been considered to be supportive, rather than transmissive, in the adult nervous system, recent studies have challenged this assumption by demonstrating that astrocytes possess functional neurotransmitter receptors. Astrocytes are now shown to directly modulate the free cytosolic calcium, and hence transmission characteristics, of neighboring neurons. When a focal electric field potential was applied to single astrocytes in mixed cultures of rat forebrain astrocytes and neurons, a prompt elevation of calcium occurred in the target cell. This in turn triggered a wave of calcium increase, which propagated from astrocyte to astrocyte. Neurons resting on these astrocytes responded with large increases in their concentration of cytosolic calcium. The gap junction blocker octanol attenuated the neuronal response, which suggests that the astrocytic-neuronal signaling is mediated through intercellular connections rather than synaptically. This neuronal response to local astrocytic stimulation may mediate local intercellular communication within the brain.
1,002 citations
TL;DR: Comparison with previous studies of localization of other glutamate receptor types revealed that NMDAR1 may colocalize with these other types in many neurons throughout the nervous system, implying that multiple types of NMDA receptors exist.
Abstract: NMDA receptors play key roles in synaptic plasticity and neuronal development, and may be involved in learning, memory, and compensation following injury A polyclonal antibody that recognizes four of seven splice variants of NMDAR1 was made using a C-terminus peptide (30 amino acid residues) NMDAR1 is the major NMDA receptor subunit, found in most or all NMDA receptor complexes On immunoblots, this antibody labeled a single major band migrating at M(r) = 120,000 The antibody did not cross-react with extracts from transfected cells expressing other glutamate receptor subunits, nor did it label non-neuronal tissues Immunostained vibratome sections of rat tissue showed labeling in many neurons in most structures in the brain, as well as in the cervical spinal cord, dorsal root and vestibular ganglia, and in pineal and pituitary glands Staining was moderate to dense in the olfactory bulb, neocortex, striatum, some thalamic and hypothalamic nuclei, the colliculi, and many reticular, sensory, and motor neurons of the brainstem and spinal cord The densest stained cells included the pyramidal and hilar neurons of the CA3 region of the hippocampus, Purkinje cells of the cerebellum, supraoptic and magnocellular paraventricular neurons of the hypothalamus, inferior olive, red nucleus, lateral reticular nucleus, peripheral dorsal cochlear nucleus, and motor nuclei of the lower brainstem and spinal cord Ultrastructural localization of immunostaining was examined in the hippocampus, cerebral cortex, and cerebellar cortex The major staining was in postsynaptic densities apposed by unstained presynaptic terminals with round or mainly round vesicles, and in associated dendrites The pattern of staining matched that of previous in situ hybridization but differed somewhat from that of binding studies, implying that multiple types of NMDA receptors exist Comparison with previous studies of localization of other glutamate receptor types revealed that NMDAR1 may colocalize with these other types in many neurons throughout the nervous system
874 citations
TL;DR: The biology of the recently discovered NGF-related family of neurotrophic factors and ciliary neurotrophic factor and their receptors are reviewed, especially in the context of the therapeutic potential of these factors in the treatment of neurological disorders of the CNS.
801 citations
TL;DR: In this paper, the authors propose a method to identify the root cause of a problem.Abbreviations: [2]... ].., [3]
674 citations
TL;DR: It is reported that mice lacking neurotrophin-3 have severe deficits in sensory and sympathetic populations and motor neurons, the enteric nervous system, and the major anatomical regions of the central nervous system seem to develop normally.
Abstract: During development, neurotrophins help shape the nervous system by regulating neuronal survival and differentiation. Neurotrophin-3 (refs 1-5) is the most abundant neurotrophin during early development. Neurons responsive to neurotrophin-3 in vitro include primary sensory, sympathetic, motor, enteric, locus coeruleus, hippocampal and cerebellar neurons (ref. 9 for example). Here we report that mice lacking neurotrophin-3 have severe deficits in sensory and sympathetic populations. These mice lack muscle spindles and show abnormal limb positions. In contrast, motor neurons, the enteric nervous system, and the major anatomical regions of the central nervous system seem to develop normally. Comparisons with mutants deficient in other neurotrophins or their receptors indicate that some neurons require more than one neurotrophin during embryogenesis and suggest that neurotrophin-3 functions by binding receptors in addition to its primary receptor trkC (ref. 16). In particular, neurotrophin-3 is essential for survival of sympathetic and sensory neurons that later become dependent on nerve growth factor or brain-derived neurotrophic factor.
648 citations
TL;DR: In vivo evidence is provided that gp120 plays a key part in HIV-1-associated nervous system impairment and this model should facilitate the evaluation and development of therapeutic strategies aimed at HIV–brain interactions.
Abstract: MANY people infected with human immunodeficiency virus type 1 (HIV-1) develop neurological complications that can culminate in dementia and paralysis1. The discrepancy between the severity of impairment and the paucity of detectable HIV-1 within neurons has led to an intense search for diffusible virus- and host-derived factors that might be neurotoxic (see ref. 2 for review). The HIV-1 envelope glycoprotein gp120 is an extracellular protein that is shed from infected cells3 and so has the potential to diffuse and interact with distant uninfected brain cells. Studies on cultured immature cells suggest that gp120 induces neurotoxicity (reviewed in refs 2, 4), and systemic injection of gp120 in neonatal rats5 and intracerebroventricular injection in adult rats results in deleterious effects on the brain6,7. To assess the pathogenic potential of gp120 in the intact brain, we have now produced gp120 in the brains of transgenic mice and found a spectrum of neuronal and glial changes resembling abnormalities in brains of HIV-1-infected humans. The severity of damage correlated positively with the brain level of gp120 expression. These results provide in vivo evidence that gp120 plays a key part in HIV-1-associated nervous system impairment. This model should facilitate the evaluation and development of therapeutic strategies aimed at HIV–brain interactions.
644 citations
TL;DR: Recent findings have started to unravel the operation of central GABA synapses where inhibitory events appear to result from the synchronous opening of only tens of GABAA receptors activated by a saturating concentration of GABA.
TL;DR: Immunostained sections of rat brain showed significant staining throughout the nervous system, including olfactory bulb, cerebral cortex, hippocampus, caudate- putamen, and many brainstem nuclei, as well as in neurons of spinal cord and sensory ganglia, supporting the presence of functional NR1/NR2 complexes throughout the nerve system.
Abstract: Neuronal plasticity associated with learning, memory and development is controlled, in part, by NMDA receptors, which are complexes consisting of the subunit NMDAR1 (NR1) and one or more NMDAR2 subunits (NR2A-NR2D). We made a polyclonal antibody to a C-terminus peptide of NR2A. In analysis of transfected cell membranes, this antibody recognizes NR2A and NR2B, and to a slight extent, NR2C and NR2D. In Western blots of rat brain, the antibody labeled a single band that comigrated with NR2A and NR2B. This antibody (NR2A/B) did not cross-react with extracts from transfected cells expressing other glutamate receptor subunits, nor did it label non-neuronal tissues. Immunostained sections of rat brain showed significant staining throughout the nervous system, including olfactory bulb, cerebral cortex, hippocampus, caudate-putamen, and many brainstem nuclei, as well as in neurons of spinal cord and sensory ganglia. This widespread distribution of staining was similar to that found with an antibody to NR1, supporting the presence of functional NR1/NR2 complexes throughout the nervous system. In the cerebellum, in contrast to staining with NR1 antibody, Purkinje cell staining with NR2A/B antibody was low, indicating that these neurons may lack functional NMDA receptors. EM examination revealed dense staining in dendrites and postsynaptic densities in cerebral cortex and hippocampus, similar to those seen with antibody to NR1. Since functional NMDA receptor complexes at synapses appear to require both NR1 and NR2 subunit proteins for full function, this study provides structural evidence for functional NR1/NR2 receptors in vivo in the nervous system.
Book•
01 Jan 1994
TL;DR: Human embryology and developmental biology , Human embryologyand developmental biology, کتابخانه دیجیتال جندی شاپور اهواز
Abstract: Carnegie Stages of Early Human Embryonic Development (Weeks 1-8) Major Developmental Events During the Fetal Period Part I: Early Development and the Fetal-Maternal Relationship Chapter 1: Getting Ready for Pregnancy Gametogenesis Preparation of the Female Reproductive Tract For Pregnancy Hormonal Interactions Involved with Reproduction in Males Chapter 2: Transport of Gametes and Fertilization Ovulation and Egg and Sperm Transport Fertilization Chapter 3: Cleavage and Implantation Cleavage Embryo Transport and Implantation Chapter 4: Molecular Basis for Embryonic Development Fundamental Molecular Processes in Development Chapter 5: Formation of Germ Layers and Early Derivatives Two-Germ-Layer Stage Gastrulation and the Three Embryonic Germ Layers Induction of the Nervous System Cell Adhesion Molecules Chapter 6: Establishment of the Basic Embryonic Body Plan Development of the Ectodermal Germ Layer Development of the Mesodermal Germ Layer Development of the Endodermal Germ Layer Basic Structure of the 4-Week Old Embryo Chapter 7: Placenta and Extraembryonic Membranes Extraembryonic Tissues Chorion and Placenta Placenta After Birth Placenta and Membranes in Multiple Pregnancies Chapter 8: Developmental Disorders: Causes, Mechanisms, and Patterns General Principles Causes of Malformations Developmental Disturbances Resulting in Malformations Part II: Development of the Body Systems Chapter 9: Integumentary, Skeletal and Muscular Systems Integumentary System Skeleton Muscular System Chapter 10: Limb Development Initiation of Limb Development Regulative Properties and Axial Determination Outgrowth of the Limb Bud Morphogenetic Control of Early Limb Development Development of Limb Tissues Chapter 11: Nervous System Establishment of the Nervous System Early Shaping of the Nervous System Histogenesis Within the Central Nervous System Craniocaudal Pattern Formation and Segmentation Peripheral Nervous System Autonomic Nervous System Later Structural Changes in the Central Nervous System Ventricles, Meninges, and Cerebrospinal Fluid Formation Cranial Nerves Development of Neural Function Chapter 12: Neural Crest Origins of the Neural Crest Migrations of the Neural Crest Differentiation of Neural Crest Cells Major Divisions of the Neural Crest Trunk Neural Crest Circumpharyngeal Neural Crest Cranial Neural Crest Chapter 13: Sense Organs Eye Ear Chapter 14: Head and Neck Early Development of the Head and Neck Fundamental Organization of the Pharyngeal Region Development of the Facial Region Development of the Pharynx and Its Derivatives Chapter 15: Digestive and Respiratory Systems and Body Cavities Digestive System Respiratory System Body Cavities Chapter 16: Urogenital System Urinary System Genital System Sexual Duct System External Genitalia Chapter 17: Cardiovascular System Developmental of the Vascular System Developmental and Partitioning of the Heart Initiation of Cardiac Function Fetal Circulation Chapter 18: Fetal Period and Birth Growth and Form of the Fetus Fetal Physiology Parturition Adaptations to Postnatal Life Overview Answers to Clinical Vignettes and Review Questions
TL;DR: The cloning and molecular identification of two putative ATP receptors supports the previously established pharmacological receptor classifications and places into perspective the evidence for ATP as a neural signalling substance by examining sites of storage, release and hydrolysis, as well as potential actions and targets.
TL;DR: This work applied the gene targeting to the NMDAR1 gene and created a mutant mouse that lacks functional NMDA receptors, providing a direct demonstration of the involvement of the NMDA receptor in the formation of periphery-related neural patterns in the mammalian brain.
TL;DR: The cloning of neurotrophin-6 (NT-6), a new mem-ber of this family from the teleost fish Xiphophorus is reported, which has a spectrum of actions similar to NGF on chick sympathetic and sensory neurons, albeit with a lower potency.
Abstract: During vertebrate development, many neurons depend for survival and differentiation on their target cells The best documented mediator of such a retrograde trophic action is the neurotrophin nerve growth factor (NGF) NGF and the other known members of the neurotrophin family, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) are conserved as distinct genes over large evolutionary distances Here we report the cloning of neurotrophin-6 (NT-6), a new member of this family from the teleost fish Xiphophorus NT-6 distinguishes itself from the other known neurotrophins in that it is not found as a soluble protein in the medium of producing cells The addition of heparin (but not chondroitin) effects the release of NT-6 from cell surface and extracellular matrix molecules Recombinant purified NT-6 has a spectrum of actions similar to NGF on chick sympathetic and sensory neurons, albeit with a lower potency NT-6 is expressed in the embryonic valvulla cerebelli; expression persists in some adult tissues The interaction of NT-6 with heparin-binding molecules may modulate its action in the nervous system
Book•
01 Feb 1994TL;DR: The techniques available for studying cells in situ bring new insights to the cellular and molecular interactions among macrophages and microglia and the other components of the nervous system.
Abstract: Publisher Summary This chapter reviews the distribution and specialized differentiation of macrophages in the nervous system, in the normal state and following injury. Macrophages are hematopoietic cells that form a long-lived resident population of cells within tissues. Macrophages are generated in the bone marrow, enter the circulation as monocytes, and then migrate into almost all tissues of the body. Mature macrophages are highly responsive to their microenvironment, differing in their morphology and expression of cell surface receptors, the repertoire of substances they secrete, and their functional capabilities. These phenotypic differences of resident macrophages depend on their interactions with other tissue cells and on the surface or substrate to which they are bound. Under the influence of unidentified factors within the central nervous system (CNS), they develop into the morphologically and phenotypically distinct microglia. Following injury to the CNS, resident and recruited mononuclear phagocytes are prominent components of the cellular response. The techniques available for studying cells in situ bring new insights to the cellular and molecular interactions among macrophages and microglia and the other components of the nervous system.
TL;DR: The unravelling of the cellular mechanisms involved in chronic pain offers the potential for developing novel therapeutic strategies, which reduce functional synaptic plasticity and prevent central atrophic and regenerative responses in injured neurones, and illustrates the capacity of the adult nervous system for maladaptive modification.
TL;DR: The transient expression of neuronal NOS may reflect a role in developmental processes such as programmed cell death, and in other neuronal sites NOS staining appears after cell bodies cease dividing and cells extend processes, and the staining persists in adult life.
TL;DR: Observed alterations provide evidence for extensive plastic reorganization in the adult human cortex following nervous system injury, but they are not a sufficient cause of the phantom phenomenon termed 'facial remapping'.
Abstract: MAGNETIC source imaging revealed that the topographic representation in the somatosensory cortex of the face area in upper extremity amputees was shifted an average of 1.5 cm toward the area that would normally receive input from the now absent nerves supplying the hand and fingers. Observed alterat
TL;DR: The data presented here indicate that long-term potentiation can be communicated between synapses on neighboring neurons by means of a diffusible messenger, which provides a mechanism for the cooperative strengthening of proximal synapses and may underlie a variety of plastic processes in the nervous system.
Abstract: The long-lasting increase in synaptic strength known as long-term potentiation has been advanced as a potential physiological mechanism for many forms of both developmental and adult neuronal plasticity. In many models of plasticity, intercellular communication has been proposed to account for observations in which simultaneously active neurons are strengthened together. The data presented here indicate that long-term potentiation can be communicated between synapses on neighboring neurons by means of a diffusible messenger. This distributed potentiation provides a mechanism for the cooperative strengthening of proximal synapses and may underlie a variety of plastic processes in the nervous system.
TL;DR: The partially overlapping expression pattern with that of cellular retinoid binding proteins suggests that B-FABP is involved in the metabolism of a so far unknown hydrophobic ligand with potential morphogenic activity during CNS development.
Abstract: Fatty acid binding proteins (FABPs) are a multigene family of small intracellular proteins that bind hydrophobic ligands. In this report we describe the cloning and expression pattern of a novel member of this gene family that is specifically expressed in the developing and adult nervous system and thus was designated brain (B)-FABP. B-FABP is closely related to heart (H)-FABP with 67% amino acid identity. B-FABP expression was first detected at mouse embryonic day 10 in neuroepithelial cells and its pattern correlates with early neuronal differentiation. Upon further development, B-FABP was confined to radial glial cells and immature astrocytes. B-FABP mRNA and protein were found in glial cells of the peripheral nervous system such as satellite cells of spinal and cranial ganglia and ensheathing cells of the olfactory nerve layer from as early as embryonic day 11 until adulthood. In the adult mouse brain, B-FABP was found in the glia limitans, in radial glial cells of the hippocampal dentate gyrus and Bergman glial cells. These findings suggest a function of B-FABP during neurogenesis or neuronal migration in the developing nervous system. The partially overlapping expression pattern with that of cellular retinoid binding proteins suggests that B-FABP is involved in the metabolism of a so far unknown hydrophobic ligand with potential morphogenic activity during CNS development.
TL;DR: PAF was detected at high levels in CSF of HIV-1-infected patients with immunosuppression and signs of CNS dysfunction, providing new insights into how HIV- 1 causes neurological impairment and how it may ultimately be ameliorated.
Abstract: The pathogenesis of central nervous system disease during human immunodeficiency virus type 1 (HIV-1) infection revolves around productive viral infection of brain macrophages and microglia. Neuronal losses in the cortex and subcortical gray matter accompany macrophage infection. The question of how viral infection of brain macrophages ultimately leads to central nervous system (CNS) pathology remains unanswered. Our previous work demonstrated high-level production of tumor necrosis factor alpha, interleukin 1 beta, arachidonic acid metabolites, and platelet-activating factor (PAF) from HIV-infected monocytes and astroglia (H. E. Gendelman, P. Genis, M. Jett, and H. S. L. M. Nottet, in E. Major, ed., Technical Advances in AIDS Research in the Nervous System, in press; P. Genis, M. Jett, E. W. Bernton, H. A. Gelbard, K. Dzenko, R. Keane, L. Resnick, D. J. Volsky, L. G. Epstein, and H. E. Gendelman, J. Exp. Med. 176:1703-1718, 1992). These factors, together, were neurotoxic. The relative role(s) of each of these candidate neurotoxins in HIV-1-related CNS dysfunction was not unraveled by these initial experiments. We now report that PAF is produced during HIV-1-infected monocyte-astroglia interactions. PAF was detected at high levels in CSF of HIV-1-infected patients with immunosuppression and signs of CNS dysfunction. The biologic significance of the results for neurological disease was determined by addition of PAF to cultures of primary human fetal cortical or rat postnatal retinal ganglion neurons. Here, PAF at concentrations of > or = 300 pg/ml produced neuronal death. The N-methyl-D-aspartate receptor antagonist MK-801 or memantine partially blocked the neurotoxic effects of PAF. The identification of PAF as an HIV-1-induced neurotoxin provides new insights into how HIV-1 causes neurological impairment and how it may ultimately be ameliorated.
TL;DR: The ability of neurotrophic factors to regulate developmental neuronal survival and adult nervous system plasticity suggests the use of these molecules to treat neurodegeneration associated with human diseases.
Abstract: The ability of neurotrophic factors to regulate developmental neuronal survival and adult nervous system plasticity suggests the use of these molecules to treat neurodegeneration associated with human diseases. Solid rationales exist for the use of NGF and neurotrophin-3 in the treatment of neuropathies of the peripheral sensory system, insulin-like growth factor and ciliary neurotrophic factor in motor neuron atrophy, and NGF in Alzheimer's disease. Growth factors have been identified for neurons affected in Parkinson's disease, Huntington's disease, and acute brain and spinal cord injury. Various strategies are actively pursued to deliver neurotrophic factors to the brain, and develop therapeutically useful molecules that mimic neurotrophic factor actions or stimulate their production or receptor mechanisms.
Journal Article•
TL;DR: Much structural information has been obtained that contributes to better understand some important aspects of vertebrate neurogenesis, particularly those related to selective cell survival in a very diverse cellular system like the nervous system.
Abstract: NGF, BDNF, NT-3, and NT-4/5 are all members of a structurally related family of molecules that function to prevent the death of embryonic neurons during development. The presence of these molecules in the targets of innervating neurons is likely to explain at least in part why many neurons depend on their target tissues for survival. A small family of related membrane proteins with a ligand-activable tyrosine kinase and expressed in the nervous system represents a significant part of the structural basis explaining how neurons discriminate between the neurotrophins and transduce the consequence of neurotrophin binding. Thus, much structural information has been obtained that contributes to better understand some important aspects of vertebrate neurogenesis, particularly those related to selective cell survival in a very diverse cellular system like the nervous system. Future studies will have to explain how the role of these molecules has to be understood in the context of the characteristic features of the nervous system, in particular neurotransmission and electrical activity. Finally, while the role of neurotrophins has been discussed here in the context of the developing nervous system, it will be important to understand what functions these molecules might play in the central nervous system. For example, neurotrophins might function as long term mediators of changes in cellular shapes under the influence of electrical activity, as well as in pathological situations when axonal elongation is needed to restore connections, or to maintain the well-being of neurons that are eliminated during the course of neurodegenerative diseases.
TL;DR: Not only can the morphology and immunoreactivity of glial cells be modulated by gonadal steroids, but a close negative correlation between the number of synapses and the amount ofglial ensheathing of a neuron has been demonstrated, suggesting an active participation of these cells in this process.
TL;DR: In situ hybridization shows that mGATA-3 mRNA accumulation is temporally and spatially regulated during early development, and at least two regulatory elements appear to be required for appropriate tissue-restricted regulation after transfection of mGata-3-directed reporter genes into cells that naturally express GATA- 3 (T lymphocytes and neuroblastoma cells).
Abstract: We describe the embryonic expression pattern as well as the cloning and initial transcriptional regulatory analysis of the murine (m) GATA-3 gene. In situ hybridization shows that mGATA-3 mRNA accumulation is temporally and spatially regulated during early development: although found most abundantly in the placenta prior to 10 days of embryogenesis, mGATA-3 expression becomes restricted to specific cells within the embryonic central nervous system (in the mesencephalon, diencephalon, pons and inner ear) later in gestation. GATA-3 also shows a restricted expression pattern in the peripheral nervous system, including terminally differentiating cells in the cranial and sympathetic ganglia. In addition to this distinct pattern in the nervous system, mGATA-3 is also expressed in the embryonic kidney and the thymic rudiment, and further analysis showed that it is expressed throughout T lymphocyte differentiation. To begin to investigate how this complex gene expression pattern is elicited, cloning and transcriptional regulatory analyses of the mGATA-3 gene were initiated. At least two regulatory elements (one positive and one negative) appear to be required for appropriate tissue-restricted regulation after transfection of mGATA-3-directed reporter genes into cells that naturally express GATA-3 (T lymphocytes and neuroblastoma cells). Furthermore, this same region of the locus confers developmentally appropriate expression in transgenic mice, but only in a subset of the tissues that naturally express the gene.
TL;DR: A three‐dimensional description of the distribution and organization of the canine intrinsic cardiac nervous system was developed in order to characterize its full extent physiologically.
Abstract: Background: A three-dimensional description of the distribution and organization of the canine intrinsic cardiac nervous system was developed in order to characterize its full extent physiologically.
Methods: The anatomy of the canine intrinsic cardiac nervous system was investigated in 67 mongrel dogs by means of visulization following methylene blue staining as well as by light and electron microscopic analyses.
Results: Collections of ganglia associated with nerves, i.e., ganglionated plexuses, were identified in specific locations in epicardial fat and cardiac tissue. Distinct epicardial ganglionated plexuses were consistently observed in four atrial and three ventricular regions, with occasional neurons being located throughout atrial and ventricular tissues. One ganglionated plexus extended from the ventral to dorsal surfaces of the right atrium. Another ganglionated plexus, with three components, was identified in fat on the left atrial ventral surface. A ganglionated plexus was located on the mid-dorsal surface of the two atria, extending ventrally in the interatrial septum. A fourth atrial ganglionated plexus was located at the origin of the inferior vena cava extending to the dorsal caudal surface of the two atria. On the cranial surface of the ventricles a ganglionated plexus that surrounded the aortic root was identified. This plexus extended to the right and left main coronary arteries and origins of the ventral descending and circumflex coronary arteries. Two other ventricular ganglionated plexuses were identified adjacent to the origins of the right and left marginal coronary arteries. Intrinsic cardiac ganglia ranged in size from ones comprising one or a few neurons along the course of a nerve to ones as large as 1 × 3 mm estimated to contain a few hundred neurons. Intrinsic cardiac neuronal somata varied in size and shape, up to 36% containing multiple nucleoli. Electron microscopic examination demonstrated typical autonomic neurons and satellite cells in intrinsic cardiac ganglia. Many of their axon profiles contained large numbers of clear, round, and dense-core vesicles. Asymmetrical axodendritic synapses were common.
Conclusions: The canine intrinsic cardiac nervous system contains a variety of neurons interconnected via plexuses of nerves, the distribution of which is wider than previously assumed. © 1994 Wiley-Liss, Inc.
TL;DR: CSPGs and associated extracellular matrix components in the preplate/subplate do not form a barrier to axonal initiation or outgrowth in the neocortex as they may in other locations and their distribution suggests a role in defining discrete axonal pathways during early cortical development.
Abstract: The distinct axonal tracts of the mature nervous system are defined during development by sets of substrate-bound and diffusible molecular signals that promote or restrict axonal elongation. In the adult cerebral cortex, efferent and afferent axons are segregated within the white matter. To define the relationship of growing efferent and afferent axons in the developing murine cortex to chondroitin sulfate proteoglycans (CSPGs) in the pericellular and extracellular matrix, we used the fluorescent tracer Dil to determine axonal trajectories and immunolabeling to disclose the distribution of CSPGs. Axons of neurons in the preplate are the first to leave the cortex; they arise in the CSPG-rich preplate and extend obliquely across it to enter the CSPG-poor intermediate zone. Slightly later, axons of cortical plate neurons extend directly across the CSPG-rich subplate, and then turn abruptly to run in the upper intermediate zone. In contrast, once afferent axons from the thalamus reach the developing cortical wall, their intracortical trajectory is centered on the CSPG-rich subplate, above the path taken by efferent axons. Our findings demonstrate a molecular difference between the adjacent but distinct efferent and afferent pathways in developing neocortex. Early efferents cross the subplate and follow a pathway that contains very little CSPG, while afferents preferentially travel more superficially within the CSPG-rich subplate. Thus, CSPGs and associated extracellular matrix (ECM) components in the preplate/subplate do not form a barrier to axonal initiation or outgrowth in the neocortex as they may in other locations. Instead, their distribution suggests a role in defining discrete axonal pathways during early cortical development.