The glycinergic inhibitory synapse

Glycine is one of the most important inhibitory neurotransmitters in the spinal cord and the brainstem, and glycinergic synapses have a well-established role in the regulation of locomotor behavior. Research over the last 15 years has yielded new insights on glycine neurotransmission. Glycinergic synapses are now known not to be restricted to the spinal cord and the brainstem. Presynaptic machinery for glycine release and uptake, the structure and function of postsynaptic receptors and the factors (both pre- and postsynaptic) which control the strength of glycinergic inhibition have been extensively studied. It is now established that glycinergic synapses can be excitatory in the immature brain and that some inhibitory synapses can corelease γ-aminobutyric acid (GABA) and glycine. Moreover, the presence of glycine transporters on glial cells and the capacity of these cells to release glycine suggest that glycine may also act as a neuromodulator. Extensive molecular studies have revealed the presence of distinct subtypes of postsynaptic glycine receptors with different functional properties. Mechanisms of glycine receptors aggregation at postsynaptic sites during development are better understood and functional implications of variation in receptor number between postsynaptic sites are partly elucidated. Mutations of glycine receptor subunits have been shown to underly some human locomotor disorders, including the startle disease. Clearly, recent work on glycine receptor channels and the synapses at which they mediate inhibitory signalling in both young and adult animals necessitates an update of our vision of glycinergic inhibitory transmission. Received 8 September 2000; received after revision 1 December 2000; accepted 21 December 2000     

Criteria for the appearance of post-tetanic potentiation of transmission at central synapses inHelix aspersa

Summary Long-lasting potentiation of inhibitory post-synaptic potentials occurs at 2 identifiable synapses inHelix brain. It appears only after tetanic stimulation and after a minimum of 20 impulses. Its amplitude and duration depend on the number of stimuli.     

Über neue elektronenmikroskopische Befunde zur peripheren vegetativen Synapse am mesenterialen Lymphgefäss vom Meerschweinchen (Cavia porcellus)

Summary Electron microscopic investigations of innervation of the mesenteric lymphatic vessels ofCavia porcellus demonstrate that, besides membrane contacts between Axon and smooth muscle cell, a local direct plasmatic connection from the nature of synapses between the nerve and the effector cell have to be considered. From this study it has been concluded that also this neuromuscular junction is a transitoric structure and not a static connection comparable to the synapses in the motor end-plate of the striated muscle.

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Die Arbeit wurde in dem elektronenmikroskopischen Laboratorium des Pathologischen Institutes Mainz unter Leitung von Priv. Doz. Dr.R. Bässler durchgeführt.     

Cytological evidence suggestive of crossing over within the mammalianX chromosome

Résumé La morphologie du chromosomeX pendant prophase I dans le mâle deSaimiri boliviensis, Macaca mulatta, Galago demidovii etTarsius syrichta suggère l'existence des synapses dans le chromosomeX des mammifères due à la possible existence d'une duplication dans ce chromosome.     

Kinetic characterization of acetylcholinesterase of muscle and rat brain

Résumé La présente étude a rélévé chez le rat des différences entre l'AChE du cerveau et celle du muscle, en ce qui concerne les pH optima, la température d'inactivation, le Km, les courbes de saturation et la réponse aux inhibiteurs. L'existence de sites allostériques différents dans l'enzyme des deux organes a aussi été observée. L'auteur suggère que ces propriétés cinétiques distinctes tiennent, en partie du moins, à des différences histophysiologiques entre les synapses de ces deux tissus.     

An evolutionarily conserved mechanism for presynaptic trapping

Presynaptic differentiation takes place over three interrelated acts involving the biogenesis and trafficking of molecular complexes of active zone material, the “trapping” or stabilization of active zone sites, and the subsequent development of mature synapses. Although the identities of proteins involved with establishing presynaptic specializations have been increasingly delineated, the exact functional mechanisms by which the active zone is assembled remain poorly understood. Here, we discuss a theoretical model for how the trapping stage of presynaptic differentiation might occur in developing neurons. We suggest that subsets of active zone proteins containing polyglutamine domains undergo concentration-dependent prion-like conversions as they accumulate at the plasma membrane. This conversion might serve to aggregate the proteins into a singular structure, which is then able to recruit scaffolding agents necessary for regulated synaptic transmission. A brief informatics analysis in support of this ‘Q’ assembly hypothesis—across commonly used models of synaptogenesis—is presented.     

Making more synapses: a way to store information?

Although information may be stored in the brain as changes in the strength of existing synapses, formation of new synapses has long been thought of as an additional substrate for memory storage. The identification of subcellular structural changes following learning in mammals poses a serious ‘needle-in-the-haystack’ problem. In most attempts to demonstrate structural plasticity during learning, animals have been exposed for prolonged periods to complex environments, where they are confronted with a variety of sensory, motor and spatial challenges throughout the exposure period. These environments are thought to promote several forms of learning. Repeated exposure to such environments has been shown to increase the density of spines and dendritic complexity in relevant brain structures. The number of neurons has also been reported to increase in some areas. It is not clear, however, whether the new synapses emerging from these forms of plasticity mediate specific information storage, or whether they reflect a more general sophistication of the excited parts of the network.     

The number of parallel fibre-Purkinje dendrite synapses. A morphometric evaluation

Summary Quantitative parameters concerning synapses were studied in the cerebellar molecular layer of 4 cats using ultrastructural morphometric methods. The number of parallel fibre-Purkinje dendrite synapses was estimated to be about 200,000.This study was granted by I.N.I.C. (Centro de Morfologia Experimental—MbP₁ e Centro de Anatomia Patológica e Oncologia-MbP₃).The authors thank Mrs M.L. Brito, Mrs M.A. Nascimento, Mrs M.G. Rodrigues and Mr L.B. Nunes for their technical assistance.     

An ultrastructural study of the synaptic glomeruli in the intermediolateral nucleus of the rat

Résumé On a constaté que le neuroptile du noyau intermédio-latéral du rat contient de nombreux glomérules synaptiques gliaux encapsulés dans lesquels se trouve habituellement un dentrite ou axe terminal très visible surmonté par de petits boutons et des dentrites. Les glomérules sont accompagnés de synapses axo-axonaux qui peuvent être le corrolaire structural d'une inhibition présynaptique. La signification fonctionnelle des glomérules et des synapses axo-axonaux est discutée.

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It is a pleasure to acknowledge the technical assistance of Mr.H. L. Chan.     

Roles of postsynaptic density-95/synapse-associated protein 90 and its interacting proteins in the organization of synapses

Synapses are central stages for neurotransmission. Neurotransmitters are released from the presynaptic membrane of one neuron, and bind to the receptors accumulated at the postsynaptic membrane, followed by the activation of the other neuron. The strength of a synapse is modified depending on the history of the previous neurotransmissions. This property is called synaptic plasticity and is implicated in learning and memory. Synapses contain not only the components essential for neurotransmission but also the signalling molecules involved in synaptic plasticity. The elucidation of the molecular structures of synapses is one of the key steps to understand the mechanism of learning and memory. Recent studies have revealed postsynaptic density (PSD)-95/synapse-associated protein (SAP) 90 as a core component in the architecture of synapses. In this review, we summarize up-to-date information about PSD-95/SAP90 and its interacting proteins, and the organization of synapses orchestrated     

Non-synaptic chemical neurotransmission.

Images with apparently gemmulofugal polarity in the EPL of the olfactory bulb are the result of sectioning, along misleading planes, gemmulopetal synapses containing postsynaptic vesicles. Unless one accepts a bidirectional conduction for chemical synapses, the internal granule cells lack actual gemmulofugal synapses and the neurotransmitter contained on their vesicles must act at non-synaptic membranes.     

The number of parallel fibre-Purkinje dendrite synapses. A morphometric evaluation.

Quantitative parameters concerning synapses were studied in the cerebellar molecular layer of 4 cats using ultrastructural morphometric methods. The number of parallel fibre-Purkinje dendrite synapses was estimated to be about 200,000.     

The role of endosomal-recycling in long-term potentiation

Long-term potentiation (LTP) defines persistent increases in neurotransmission strength at synapses that are triggered by specific patterns of neuronal activity. LTP, the most widely accepted molecular model for learning, is best characterised at glutamatergic synapses on dendritic spines. In this context, LTP involves increases in dendritic spine size and the insertion of glutamate receptors into the post-synaptic spine membrane, which together boost post-synaptic responsiveness to neurotransmitters. In dendrites, the material required for LTP is sourced from an organelle termed the endosomal-recycling compartment (ERC), which is localised to the base of dendritic spines. When LTP is induced, material derived from the recycling compartment, which contains α-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptors (AMPARs), is mobilised into dendritic spines feeding the increased need for receptors and membrane at the spine neck and head. In this review, we discuss the importance of endosomal-recycling and the role of key proteins which control these processes in the context of LTP.     

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.     

Non-synaptic chemical neurotransmission

Summary Images with apparently gemmulofugal polarity in the EPL of the olfactory bulb are the result of sectioning, along misleading planes, gemmulopetal synapses containing postsynaptic vesicles. Unless one accepts a bidirectional conduction for chemical synapses, the internal granule cells lack actual gemmulofugal synapses and the neurotransmitter contained in their vesicles must act at non-synaptic membranes.Supported by grant MA4183 of the Medical Research Council of Canada.     

慢性酒精中毒小鼠小脑的超微结构实验研究

目的 探讨慢性酒精中毒导致神经系统损伤的机制.方法 建立小鼠慢性酒精中毒动物模型,观察动物行为学的改变,测量血浆酒精浓度,通过透射电镜了解小脑的超微结构变化.结果 酒精处理组的血浆酒精浓度为101.4±20.5 mg/dL,与对照组和配对对照组比较,酒精处理组小鼠行动欠灵活,小脑线粒体形状多样、大小多变、数量增加和平均横断面面积显著减小;突触的数量减少、突触后膜致密物质厚度变薄、突触活性区长度变短及突触间隙宽度变宽,突触前结构内附着于突触的囊泡较多.结论 酒精对线粒体和突触结构、功能的损害可能是慢性酒精中毒的神经系统损伤机制之一.     

Synapse elimination in the developing cerebellum

Neural circuits in neonatal animals contain numerous redundant synapses that are functionally immature. During the postnatal period, unnecessary synapses are eliminated while functionally important synapses become stronger and mature. The climbing fiber (CF) to the Purkinje cell (PC) synapse is a representative model for the analysis of postnatal refinement of neuronal circuits in the central nervous system. PCs are initially innervated by multiple CFs with similar strengths around postnatal day 3 (P3). Only a single CF is selectively strengthened during P3–P7 (functional differentiation), and the strengthened CF undergoes translocation from soma to dendrites of PCs from P9 on (dendritic translocation). Following the functional differentiation, supernumerary CF synapses on the soma are eliminated, which proceeds in two distinct phases: the early phase from P7 to around P11 and the late phase from around P12 to P17. Here, we review our current understanding of cellular and molecular mechanisms of CF synapse elimination in the developing cerebellum.     

Increased transmission at electronic synapses and paroxysmal depolarization induced by cardiazol in the Mauthner cell]

Cardiazol induces in the Mauthner cell the paroxysmal depolarizing shifts which are characteristic of epilepsia at the neuronal level. The period of depolarizations is preceded and, later, accompanied by an increased transmission at the electrotonic synapses which are established upon this neuron by primary afferent vestibular fibers. Increased excitability of the chemical synapses occurs subsequently.     

The action of ouabain in promoting the release of catecholamines

Summary It is suggested that ouabain promotes catecholamine release by causing a rise in intracellular Na⁺ which, in turn, causes an elevated steady-state level of intracellular Ca²⁺. It is suggested that the Na⁺–K⁺-ATPase is not directly involved in exocytosis at either adrenergic or cholinergic synapses.     

Localization and stabilization of ionotropic glutamate receptors at synapses

Appropriate targeting and clustering of ionotropic glutamate receptors (iGluRs) is critical for the formation and maintenance of excitatory synapses. Recent studies have demonstrated that the synaptic localization of iGluR subtypes is remarkably heterogeneous and subject to regulation over time scales ranging from minutes to months. These findings, together with the identification of key protein binding partners of iGluRs, have opened a window onto the complex cell biology of iGluR membrane trafficking. In this article, we review recent findings on the cellular and molecular mechanisms involved in localizing iGluRs at synapses and discuss their implications for synaptogenesis and synaptic plasticity.