Presynaptic Part Research Articles

Clathrin-Mediated Endocytosis in the Giant Reticulospinal Synapse in Lamprey

The chemical synapse is a key structure used by neurons to communicate with neighboring cells. This is an asymmetric structure composed of two elements. The presynaptic part contains small synaptic vesicles filled with neurotransmitter. In an active synapse synaptic vesicles fuse with the presynaptic membrane and release neurotransmitter into the synaptic cleft. This results in activation of receptor molecules and respective ion channels on the postsynaptic cell. After a fusion event, the vesicle membrane is retrieved to form a new vesicle. Clathrin-mediated endocytosis is one of the main pathways for synaptic vesicle recycling. It involves a series of steps that starts with a flat plasma membrane and ends with an internalized coated vesicle. Four distinct stages have been defined: (1) the assembly of the clathrin coat, (2) the invagination of the coated membrane into a pit, (3) the constriction of the coated pit, and (4) the fission reaction that liberates the coated vesicle (e.g. De Camilli and Takei, 1996; Brodin et al., 1997). Analysis of mutant yeast and animal cells have linked a number of proteins to each of these stages. Taken together with data from in vitro binding studies, these observations indicate the existence of a complex molecular network that regulate the endocytic reactions.

Geniculo-cortical afferents form synaptic contacts with vasoactive intestinal polypeptide (VIP) immunoreactive neurons of the rat visual cortex

The lateral geniculate nucleus of the rat was injected with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) to see if geniculo-cortical axons terminate on vasoactive intestinal polypeptide immunoreactive (VIP-IR) neurons of the primary visual cortex. PHA-L-labelled boutons attached to VIP-IR perikarya and dendrites were identified as presynaptic parts of asymmetrical synapses. This geniculo-cortical projection to VIP-IR cells in the visual cortex and comparable findings in the somatosensory cortex suggest that sensory input from specific thalamic nuclei may influence local circuit inhibition and the metabolic state within the cortical domain via VIP-IR neurons.

Axonal degeneration of ascending sensory neurons in gracile axonal dystrophy mutant mouse

The distribution of axonal spheroids was examined in the central nervous system of gracile axonal dystrophy (GAD) mutant mice. Only few spheroids are observed in the gracile nucleus of the medulla in normal mice throughout the period examined, while they are first noted in GAD mice as early as 40 days after birth. The incidence of spheroids shifts from the gracile nucleus to the gracile fasciculus of the spinal cord with the progress of disease, suggesting that the degenerating axonal terminals of the dorsal ganglion cells back from the distal presynaptic parts in the gracile nucleus, along the tract of the gracile fasciculus, toward the cell bodies in the dorsal root ganglion. This phenomenon indicates that the distribution of spheroids is age dependent and reflects a dying-back process in degenerating axons. In addition to the gracile nucleus and the gracile fasciculus, which is one of the main ascending tracts of primary sensory neurons, it was noted that the other primary sensory neurons joined with some of the second-order neurons at the dorsal horn and neurons at all levels of the dorsal nucleus (Clarke's column) are also severely affected in this mutant. The incidence of the dystrophic axons are further extended to the spinocerebellar tract and to particular parts of the white matter of the cerebellum, such as the inferior cerebellar peduncle and the lobules of I-III and VIII in the vermis. These results indicate that this mutant mouse is a potential animal model for human degenerative disease of the nervous system, such as neuroaxonal dystrophy and the spinocerebellar ataxia.

Structure and Cytochemistry of the Chemical Synapses

Publisher Summary This chapter describes the structure and cytochemistry of chemical synapses. The synapses provide morphologically and functionally specialized contacts for an excitatory and inhibitory action between the nerve cells and between neurons and some non-neuronal cells. Cytochemistry and autoradiography present a link among the morphological, the biochemical and physiological studies. The majority of interneuronal synapses and the neuromuscular junctions in vertebrates are chemical synapses. Structurally, they have three basic components, which are the presynaptic part, the synaptic cleft, and the postsynaptic part. The other organelles and inclusions in the axonal endings probably have no specific role in the synaptic transmission as they are not found in all cases in the presynaptic element. Both cell membranes, which realize the direct conduction of bioelectrical information, the presynaptic and postsynaptic membranes, are highly organized membrane systems, with corresponding structure, cytochemical characteristics, and enzyme equipment. The definite arrangement of the acidic and basic groups on the presynaptic and postsynaptic elements probably plays a determining role in the formation of the synaptic contacts during synaptogenesis.

The non-impulsive stretch-receptor complex of the crab: a study of depolarization-release coupling at a tonic sensorimotor synapse

A new preparation for the study of synaptic transmission is described from the thoracic ganglion of the crabCallinectes sapidus. The central anatomy of the nonimpulsive stretch-receptor neurons of the thoracic-coxal joint and that of the promotor motoneurons with which they form synaptic junctions was studied with intracellular cobalt staining and light and electron microscopy. Attention was centred on the interaction of the stretch-receptor T-fibre and the four large motoneurons supplying the promotor muscle which have their cell-bodies on the dorsal surface of the ganglion. The presynaptic terminal region of the T-fibre appeared to be a simple cylinder in form with a diameter of 40-60 μm and containing large stores of synaptic vesicles at its periphery, opposite the complex of motoneuron dendrites. The transmission characteristics of the junctions between receptor cell and motoneurons were studied by transmembrane current injection into the isolated T-fibre by means of a sucrose gap and simultaneous intracellular recording with microelectrodes from the presynaptic terminal and the somata of postsynaptic cells. It was shown that depolarization-release coupling in the T-fibre has similar properties to those that have been demonstrated in the squid giant synapse, with the same values for ‘threshold’, peak release and ‘suppression potential’. The crab synapses differ from that of the squid in that they normally transmit prolonged, graded depolarizations (i.e. receptor potentials) which are decrementally conducted from the periphery. Consistent with this role, the junctions were found to be capable of continuous tonic transmission over many seconds without the strong depletion seen in more phasic synapses. In a study of the relation between the synaptic properties and the stretch reflex it was shown that some of the time- and amplitude-dependent behaviour of the overall reflex can be encoded at the level of the synaptic transmission, largely through the parameter of transmitter availability. Conduction of electrical signals in the proximal and presynaptic part of the sensory fibre was also investigated. Transient responses to step depolarizing currents in the fibre indicate the existence of a mechanism for the partial compensation of capacitative distortion in the decrementally conducted receptor potential. This is the first example of intracellular recording from presynaptic terminals of nonimpulsive neurons with simultaneous monitoring of postsynaptic potential changes, allowing for a direct analysis of depolarization-release coupling characteristics. The use of the preparation for further study of synaptic physiology and sensorimotor systems is discussed.

An ultrastruct study of the innervation of the musculature of the pond snail Lymnaea stagnalis (L.) with reference to peripheral neurosecretion.

The ultrastructure of nerve endings in the musculature of Lymnaea stagnalis was studied. Seventeen different types of axon ending were distinguished according to the size and morphology of the granules or vesicles they contain. Nine types of axon endings form neuromuscular synapses. Some of these types also form axo-somatic synapses on peripheral neurones. One axon may innervate several muscle cells. Furthermore more than one type of axon may innervate one muscle cell. One type of axon ending forms axo-axonic synapses on the presynaptic part of neuromuscular junctions. In the connective tissue near muscle cells seven types of free axon endings were found. These seem to be peripheral neurosecretory endings. Some of these are probably derived from known types of neurosecretory cells in the central nervous system, whereas others appear to originate from peripheral neuronal perikarya. Body wall muscles appear to be innervated by neuromusculatur synapses, whereas in the visceral musculature both neuromuscular junctions and free axon endings are found.

Ultrastructural analysis of phospholipase A induced changes in membranes of synaptic regions in rat motor cortex.

The effect of purified Naja nigricollis phospholipase A on slices from motor cortex from rat brain was analysed at an ultrastructural level. Samples stabilized directly with glutaraldehyde were compared with samples incubated in buffer with or without enzyme. Plasma membranes of nerve terminals, synaptic contact regions and synaptic vesicles were the main parameters studied. As judged by the electron microscopic technique the synaptic areas show a high resistance to the enzyme treatment. The intercellular space of the synaptic cleft seems unaltered. At the highest concentrations of the enzyme an increased density is noticed at the presynaptic part of the membrane. The extracellular space widens and nerve terminals and mitochondria become distended with increasing enzyme concentrations. The membranes all through the tissue appear ruptured to small pieces and at the highest enzyme concentrations used, altered in their structural organization. Quantitative analysis shows that the number of synaptic vesicles per unit surface area decreases, while ruptures of the plasma membranes of nerve terminals increase in number with increasing enzyme concentrations.

Degeneration and regeneration of interneuronal synapses

1. Degeneration of synapses in the cat superior cervical ganglion after division of preganglionic fibers was expressed under the optical microscope by argyrophilia or argyrophobia, hypertrophy, and lysis. Under the electron microscope, two types of changes were observed during this process (“dark” and “light” degeneration of synapses). 2. The structure of the synaptic endings in sections impregnated with silver remains similar at all stages of regeneration, although their function undergoes considerable change during this period. Electron-microscopy showed that transmission of impulses through regenerating synapses is restored only after numerous synaptic vesicles have appeared in their presynaptic parts, and active zones of pre- and postsynaptic membranes have been formed. 3. Formation of the presynaptic part of the synapse precedes specific differentiation of the postsynaptic membrane. The symmetrical type of structure of the primary contact observed in early stages of regeneration of axonal endings is replaced by formations which are indistinguishable in structure and function from ordinary synapses.

Ultrastructural appearance of glycogen in the hypothalamus of the rabbit following chlorpromazine administration.

The tuber cinereum of hypothalamus, cerebral cortex, cerebellar cortex and caudate nucleus of rabbits were examined under the electron microscope following intramuscular administration of chlorpromazine with special consideration of ultrastructural changes in amount and distribution of glycogen granules in their hypothalamus. In these regions, normal astrocytes and their processes contain glycogen granules diffusely scattered in the cytoplasm. In the neurons of the normal hypothalamus and cerebellar cortex, glycogen granules are seen in some presynaptic endings and distal parts of dendrites but not in the perikaryal cytoplasm. In the tuber cinereum of the hypothalamus, after chlorpromazine administration, abundant glycogen granules accumulate at the postsynaptic sites, especially in peripheric parts of dendrites, and clusters of glycogen granules appear in the perikaryal cytoplasm of the nerve cells. These findings are interpreted as an increase of glycogen in these cellular regions and the suggestion is made that chlorpromazine inhibits the glycolytic metabolism in the distal parts of dendrites, particularly at postsynaptic sites and in the perikarya of nerve cells of the hypothalamus.