Neocortical transplants in the rat brain: an ultrastructural study

Summary Electron microscopic analysis of neocortical transplants in the cerebellum of the host animals showed that the nerve cells, glial cells, and neuropil of the transplants were normal. These transplants showed anatomical integration with the host brain through various regions of interface. Neuropil interfaces were found to have a high density of synaptic profiles, and medullary interfaces had a very small number of synaptic profiles.Acknowledgment. Research supported by Contract No. N00014-83 from the Office of Naval Research, Department of the Navy to E.N.A., and N.I.H. Research Grant No. NS-08817 to G.D. Das.     

Human embryonic stem cell-derived neurons establish region-specific, long-range projections in the adult brain

While the availability of pluripotent stem cells has opened new prospects for generating neural donor cells for nervous system repair, their capability to integrate with adult brain tissue in a structurally relevant way is still largely unresolved. We addressed the potential of human embryonic stem cell-derived long-term self-renewing neuroepithelial stem cells (lt-NES cells) to establish axonal projections after transplantation into the adult rodent brain. Transgenic and species-specific markers were used to trace the innervation pattern established by transplants in the hippocampus and motor cortex. In vitro, lt-NES cells formed a complex axonal network within several weeks after the initiation of differentiation and expressed a composition of surface receptors known to be instrumental in axonal growth and pathfinding. In vivo, these donor cells adopted projection patterns closely mimicking endogenous projections in two different regions of the adult rodent brain. Hippocampal grafts placed in the dentate gyrus projected to both the ipsilateral and contralateral pyramidal cell layers, while axons of donor neurons placed in the motor cortex extended via the external and internal capsule into the cervical spinal cord and via the corpus callosum into the contralateral cortex. Interestingly, acquisition of these region-specific projection profiles was not correlated with the adoption of a regional phenotype. Upon reaching their destination, human axons established ultrastructural correlates of synaptic connections with host neurons. Together, these data indicate that neurons derived from human pluripotent stem cells are endowed with a remarkable potential to establish orthotopic long-range projections in the adult mammalian brain.     

Transplantation into the mammalian adult spinal cord

Summary Embryonic cerebral cortical tissue obtained from rat embryos of 15-day gestation was transplanted into the cervical spinal cord of adult rats. The cortical transplants survived, grew, and established connections with the host animal's spinal cord. In other animals, knife lesions were first made in the host's spinal cord, and then embryonic cortical tissue was transplanted into the site of the lesion. The cortical transplants in these animals were observed to become an integral part of the host animal's spinal cord.     

Transplantation of brain tissue in the brain of adult rats

Summary Brain tissues obtained from rat embryos were transplanted in the forebrain and/or cerebellum of the adult rats. The transplants survived, grew and achieved normal cellular and cytoarchitectural differentiation. They had become anatomically integrated with the host brain. The animals did not show any obviously detectable abnormal behavior or pathology of the brain. The transplants survived as long as the animals did suggesting that they had become a part and parcel of the host brain.Supported by research grants NS-08817 and CA-14650 from N.I.H.     

Comparative anatomy of the host-fungus interface in mycorrhizas

Summary There are several types of mycorrhizal symbiosis (ectomycorrhiza, endomycorrhiza, ectendomycorrhiza), and the interfaces between the host-plant and the fungal symbiont have different organizations. The interfaces between the partners are always limited on the one side by the fungal plasmalemma and on the other side by the plasmalemma of the host plant or the perisymbiont membrane derived from it The cytoplasms of the partners are therefore separated by a mixed apoplast consisting of a fungal wall and a host wall or an apposition layer.     

Transplantations interspécifiques de gonades embryonnaires de Phasianidés

Summary When indifferent gonads from red-legged partridges, Japanese quail or pintado embryos were transplanted into the coelomic cavity of early chick embryos, they differentiated into ovaries and testes, regardless of the sex of the host. Testicular transplants brought about the retrogression of both Müllerian ducts in female hosts, and ovarian transplants the feminization of the left testis in male hosts. This demonstrates hormonal activity of the embryonic gonads in the 3 species under study. Since the embryonic sex hormones show inter-specific activity, they may be of identical chemical nature.

---

---

Avec la collaboration technique deA. Zeis.     

Types of nerve terminals in fetal and neonatal rabbit myocardium

With the use of electron microscopy 4 types of axonal profiles were observed in the developing myocardium of rabbits: 1) adrenergic axons which contained mainly small dense-core vesicles and which presumably can store 5-hydroxy-dopamine; 2) cholinergic axons which contained small clear synaptic vesicles and which were acetylcholinesterase-positive; 3) axons which contained large vesicles filled with moderately electron-dense material and which resembled purinergic axons; and 4) profiles filled with mitochondria, vesicles of various sizes, lysosome-like bodies, and microtubules and which resembled sensory terminals.     

Role of grafted Schwann cells in the regeneration of intraspinal nerve fibers when peripheral nerve, skeletal muscle or submandibular gland fragments are transplanted into the spinal cord of the mouse

Small pieces of peripheral nerve, skeletal muscle or submandibular gland, taken from young or new-born mice, were grafted into the non-transected spinal cord of young albino mice, at the thoracic level, through a punctiform meningeal opening. Neighbouring intraspinal nerve fibres, severed during the grafting process, regenerate into and eventually throughout the transplants. In this regenerative process, sedentary or migrating Schwann cells of the transplants probably have a prominent influence in guiding the growth of the axonal sprouts they ensheathe and eventually myelinate.     

Effects of altered thyroid state on the inhibition produced by locus coeruleus in purkinje cells in the rat

Summary The number of cerebellar Purkinje cells inhibited after locus coeruleus stimulation was found to be greater in hyperthyroid rats than in control healthy animals; these in turn showed a higher percentage of inhibited cells than hypothyroid rats. It is concluded that thyroid hormone is capable of modulating synaptic activity in the LC-PC pathway.     

Types of nerve terminals in fetal and neonatal rabbit myocardium

Summary With the use of electron microscopy 4 types of axonal profiles were observed in the developing myocardium of rabbits: 1) adrenergic axons which contained mainly small dense-core vesicles and which presumably can store 5-hydroxydopamine; 2) cholinergic axons which contained small clear synaptic vesicles and which were acetylcholinesterase-positive; 3) axons which contained large vesicles filled with moderately electron-dense material and which resembled purinergic axons; and 4) profiles filled with mitochondria, vesicles of various sizes, lysosome-like bodies, and microtubules and which resembled sensory terminals.Supported in part by the Kentucky Heart Association and in part by the Human Development Studies Program, University of Kentucky. Excellent technical assistance of Mrs Merle Wekstein is gratefully acknowledged.     

Signaling in the Chemosensory Systems

Taste bud cells communicate with sensory afferent fibers and may also exchange information with adjacent cells. Indeed, communication between taste cells via conventional and/or novel synaptic interactions may occur prior to signal output to primary afferent fibers. This review discusses synaptic processing in taste buds and summarizes results showing that it is now possible to measure real-time release of synaptic transmitters during taste stimulation using cellular biosensors. There is strong evidence that serotonin and ATP play a role in cell-to-cell signaling and sensory output in the gustatory end organs.     

Information processing along the course of a visual interneuron

Summary Locust ocellar retinal cells are innervated by giant second order cells, 2 mm long, which show discrete zones of integration along their course, including a major zone in the axonal length of the neuron. The complex synaptic arrangements which exist between higher-order afferent and efferent cells and these second order cells along their course suggests that transmission takes place by the electrotonic spread of slow potentials. The size and accessibility of these visual interneurons offers a unique preparation for examining mechanisms of graded synaptic transmission.     

Information processing along the course of a visual interneuron.

Locust ocellar retinal cells are innervated by giant second order cells, 2 mm long, which show discrete zones of integration along their course, including a major zone in the axonal length of the neuron. The complex synaptic arrangements which exist between higher-order afferent and efferent cells and these second order cells along their course suggests that transmission takes place by the electrotonic spread of slow potentials. The size and accessibility of these visual interneurons offers a unique preparation for examining mechanisms of graded synaptic transmission.     

星形胶质细胞在学习记忆中的作用

星形胶质细胞是神经胶质细胞的主要组成部分,遍布整个神经系统.以往认为星形胶质细胞的功能主要为支持营养神经元,参与物质代谢,血脑屏障形成等等,但最近研究发现它们还可促进突触形成,影响信号传导及突触可塑性,从而在学习记忆的形成中发挥重要作用.     

Cbln and C1q family proteins – New transneuronal cytokines

The C1q family is characterized by a C-terminal conserved global C1q domain, which is structurally very similar to the tumor necrosis factor homology domain. Although some C1q family members are expressed in the central nervous system, their functions have not been well characterized. Cbln1, a member of the Cbln subfamily of the C1q family, is predominantly expressed in cerebellar granule cells. Interestingly, Cbln1 was recently shown to play two unique roles at excitatory synapses formed between cerebellar granule cells and Purkinje cells: the formation and stabilization of synaptic contact, and the control of functional synaptic plasticity by regulating the postsynaptic endocytosis pathway. Since other Cbln subfamily members, Cbln2-Cbln4, are expressed in various regions of developing and mature brains, Cbln subfamily proteins may generally serve as a new class of transneuronal regulators of synapse development and synaptic plasticity in various brain regions.     

A gelatin sponge model for studying tumor growth: quantitation of tumor cells and leukocytes in the CHO tumor

A gelatin sponge model system for tumor cell inoculation and retrieval of tumor-associated leukocytes is described. Gelatin sponges pre-implanted in nude mice harboring tumorigenic Chinese hamster ovary cells (line CHO) were examined at 2 and 11 days after injection of tumor cells for tumor cell content and leukocyte accumulation after digesting the sponge matrix in collagenase solution. The data indicate a progressive influx of host cells consisting primarily of macrophages, neutrophils and lymphocytes. The total number of viable tumor cells as well as the fraction of surviving tumor cells with clonogenic potential also increased with tumor age. Blank sponges not harboring tumor cells elicited an inflammatory response in the animals which did not change appreciably with length of sponge residence. However, when the sponges were harboring tumor cells, the accumulation of host leukocytes far exceeded that which occurred in blank sponges. This observation suggests a host response directed toward the tumor which is absent in animals bearing blank sponges. Apart from providing anchorage for injected cells, the gelatin sponge, by virtue of its digestibility in collagenase, makes possible the easy retrieval and precise quantitation of tumor-associated host cells.     

A gelatin sponge model for studying tumor growth: quantitation of tumor cells and leukocytes in the CHO tumor

Summary A gelatin sponge model system for tumor cell inoculation and retrieval of tumor-associated leukocytes is described. Gelatin sponges pre-implanted in nude mice harboring tumorigenic Chinese hamster ovary cells (line CHO) were examined at 2 and 11 days after injection of tumor cells for tumor cell content and leukocyte accumulation after digesting the sponge matrix in collagenase solution.The data indicate a progressive influx of host cells consisting primarily of macrophages, neutrophils and lymphocytes. The total number of viable tumor cells as well as the fraction of surviving tumor cells with clonogenic potential also increased with tumor age. Blank sponges not harboring tumor cells elicited an inflammatory response in the animals which did not change appreciably with length of sponge residence. However, when the sponges were harboring tumor cells, the accumulation of host leukocytes far exceeded that which occurred in blank sponges. This observation suggests a host response directed toward the tumor which is absent in animals bearing blank sponges. Apart from providing anchorage for injected cells, the gelatin sponge, by virtue of its digestibility in collagenase, makes possible the easy retrieval and precise quantitation of tumor-associated host cells.Supported by the United States Department of Energy and National Institutes of Health Grant P41-RR01315.     

Neurexins and neuroligins: synapses look out of the nervous system

The scientific interest in the family of the so-called nervous vascular parallels has been growing steadily for the past 15 years, either by addition of new members to the group or, lately, by deepening the analysis of established concepts and mediators. Proteins governing both neurons and vascular cells are known to be involved in events such as cell fate determination and migration/guidance but not in the last and apparently most complex step of nervous system development, the formation and maturation of synapses. Hence, the recent addition to this family of the specific synaptic proteins, Neurexin and Neuroligin, is a double innovation. The two proteins, which were thought to be “simple” adhesive links between the pre- and post-synaptic sides of chemical synapses, are in fact extremely complex and modulate the most subtle synaptic activities. We will discuss the relevant data and the intriguing challenge of transferring synaptic activities to vascular functions.     

Afferent fibers from the septum terminate on gamma-aminobutyric acid (GABA-) interneurons and granule cells in the area dentata of the rat

Interneurons in the area dentata of the rat were immunostained with an antibody to gamma-aminobutyric acid. After septal lesions, degenerating terminals were found in asymmetric synaptic contact with granule cell somata and dendritic elements of immunoreactive and nonreactive cells in the supragranular part of the molecular layer.     

Determination of the connectivity of newborn neurons in mammalian olfactory circuits

The mammalian olfactory bulb is a forebrain structure just one synapse downstream from the olfactory sensory neurons and performs the complex computations of sensory inputs. The formation of this sensory circuit is shaped through activity-dependent and cell-intrinsic mechanisms. Recent studies have revealed that cell-type specific connectivity and the organization of synapses in dendritic compartments are determined through cell-intrinsic programs already preset in progenitor cells. These progenitor programs give rise to subpopulations within a neuron type that have distinct synaptic organizations. The intrinsically determined formation of distinct synaptic organizations requires factors from contacting cells that match the cell-intrinsic programs. While certain genes control wiring within the newly generated neurons, other regulatory genes provide intercellular signals and are only expressed in neurons that will form contacts with the newly generated cells. Here, the olfactory system has provided a useful model circuit to reveal the factors regulating assembly of the highly structured connectivity in mammals.