-
Journal of Neurocytology Jan 1994Parallel-fibre synaptic membranes were examined by freeze-fracture and ethanolic-phosphotungstic acid methods in the cerebellum of homozygous (j/j) Gunn rats with...
Parallel-fibre synaptic membranes were examined by freeze-fracture and ethanolic-phosphotungstic acid methods in the cerebellum of homozygous (j/j) Gunn rats with hereditary jaundice. Parallel-fibre synapses with dendritic spines of Purkinje cell were severely affected since many Purkinje cells degenerated during the early postnatal period. Some parallel-fibre synaptic terminals lacked their postsynaptic partners and faced astrocytic processes from 18 days of age to the adult stage. These parallel-fibre terminals contained clusters of synaptic vesicles adjacent to synaptic membranes, and synaptic membranes and synaptic cleft materials were identical to those of parallel fibres with postsynaptic partners, as visualized by conventional electron microscopy with osmium tetroxide postfixation and staining of sections with uranyl acetate and lead citrate. In freeze-fractured specimens, the presynaptic membrane of parallel fibres had diffusely distributed large particles and tiny pits on the P-face and protuberances on the E-face, together representing synaptic vesicle attachment sites. Such vesicle attachment sites were present on the presynaptic membranes of parallel fibres without postsynaptic partners from day 18 to the adult stage. After ethanolic-phosphotungstic acid staining, parallel-fibre terminals displayed presynaptic dense projections, intercleft materials and postsynaptic thickening, but some parallel fibres lacked postsynaptic thickening. These observations suggest that the presynaptic membrane structure of the parallel fibre is preserved, even in the absence of a postsynaptic partner, in j/j cerebella. A mechanism for persistence of presynaptic membrane structures without postsynaptic partners in j/j cerebella is discussed.
Topics: Animals; Cerebellum; Ethanol; Female; Freeze Fracturing; Intracellular Membranes; Jaundice; Male; Nerve Fibers; Phosphotungstic Acid; Presynaptic Terminals; Rats; Rats, Gunn; Rats, Wistar
PubMed: 8176417
DOI: 10.1007/BF01189815 -
The Journal of Physiology May 2004Mechanisms of long-term potentiation (LTP) maintenance are discussed in the light of the phenomenon of silent synapses. Evidence that LTP is associated with the... (Review)
Review
Mechanisms of long-term potentiation (LTP) maintenance are discussed in the light of the phenomenon of silent synapses. Evidence that LTP is associated with the insertion of new AMPA receptors (AMPARs) in postsynaptically silent (deaf) synapses expressing only NMDA receptors (NMDARs) before LTP induction has led to the assumption that the debate on pre- versus postsynaptic locus of LTP expression has been resolved in favour of the latter. However, recent data indicate that these synapses are mainly presynaptically silent (mute or whispering), because the probability of glutamate release (P(r)) or glutamate concentration in the cleft is too low to activate AMPARs. In this case LTP could be explained by an increase in P(r) or enhanced glutamate concentration to activate low affinity AMPARs. Optical methods to probe calcium transients in dendritic spines have revealed an increase in P(r) during LTP with concomitant postsynaptic modifications. A hypothesis is considered that accounts for the differences in both the initial failure rates between AMPAR- and NMDAR-mediated responses, and the LTP-associated decrease in failures of AMPAR-mediated responses. According to this hypothesis, glutamate release is potentiated by the strong postsynaptic depolarization used to identify NMDAR-mediated responses. We suggest that the expression of LTP may depend on coordinated pre- and postsynaptic modifications whose relative contributions vary according to the initial state of the synapse, the experimental protocol and time after induction.
Topics: Animals; Humans; Long-Term Potentiation; Neuronal Plasticity; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Synapses; Synaptic Membranes
PubMed: 15034124
DOI: 10.1113/jphysiol.2003.058966 -
Toxicon : Official Journal of the... Oct 1994Relatively little attention has been given to the biological properties of Duvernoy's secretions produced by opisthoglyphous and some aglyphous colubrid snakes. A review... (Comparative Study)
Comparative Study Review
Relatively little attention has been given to the biological properties of Duvernoy's secretions produced by opisthoglyphous and some aglyphous colubrid snakes. A review is presented of literature pertaining to these secretions. Most detailed analyses of Duvernoy's secretions and their biological properties have been performed since the late 1970s. The dispholidines, Dispholidus typus and Thelotornis sp., and the natricines, Rhabdophis tigrinus and R. subminiata, have received the most attention due to the high toxicity of their secretions and their medical importance. These species produce secretions with variably strong prothrombin-activating activity, defibrinating activity, and hemorrhagic potential. Boigines, and natricines other than Rhabdophis, produce secretions of low to moderate toxicity and are variably hemorrhagic and proteolytic. Xenodontines and homalopsines similarly show hemorrhagic potential with low to moderate toxicity. Neurotoxic activity has been reported only from secretions of the boigines, Boiga blandingi and B. irregularis and the xenodontine, Heterodon platyrhinos. These species produce secretions containing postsynaptically acting components. Analyses of some of these secretions have shown that enzymes common to many ophidian venoms such as phospholipases A and L-amino acid oxidase are uncommon in the colubrid secretions studied. This may be due to few studies assaying for multiple enzyme activities and/or the unavailability of many secretion samples for study. Methods of secretion extraction, storage, and assay are discussed. Projected future research and the adaptive implications of Duvernoy's secretions are considered.
Topics: Animals; Chemical Fractionation; Chromatography, High Pressure Liquid; Coagulants; Colubridae; Enzymes; Exocrine Glands; Hemorrhage; Male; Mouth Mucosa; Proteins; Snake Venoms
PubMed: 7846688
DOI: 10.1016/0041-0101(94)90347-6 -
The Journal of Neuroscience : the... Sep 1981Norepinephrine is known to inhibit its own release from presynaptic nerve terminals through alpha 2-adrenergic receptors, which presumably have a presynaptic...
Norepinephrine is known to inhibit its own release from presynaptic nerve terminals through alpha 2-adrenergic receptors, which presumably have a presynaptic localization. alpha 2-Adrenergic receptors (as determined by [3H]clonidine binding) appear in rat submandibular gland membranes following reserpine treatment. These alpha 2 receptors seem to be localized postsynaptically, based on the following evidence. (1) Partial destruction of the presynaptic nerve terminals with 6-hydroxydopamine did not decrease the density of alpha 2-adrenergic receptors following subsequent reserpine administration. (2) Duct ligation, which results in atrophy of the gland, markedly decreased the density of the receptors following subsequent reserpine administration. (3) Surgical denervation resulted in the appearance of high levels of alpha 2-adrenergic receptors. (4) The changes in alpha 2 receptors paralleled the changes in postsynaptic beta-adrenergic receptor binding (as determined by [3H]dihydroalprenolol). While these results establish the existence of postsynaptic alpha 2-adrenergic receptors in an innervated tissue, the concomitant presence of a low density of presynaptic alpha 2 receptors has not been eliminated.
Topics: Animals; Cell Membrane; Clonidine; Dihydroalprenolol; Ganglia, Sympathetic; Kinetics; Male; Rats; Rats, Inbred Strains; Receptors, Adrenergic; Receptors, Adrenergic, alpha; Reserpine; Submandibular Gland; Synapses
PubMed: 6270284
DOI: 10.1523/JNEUROSCI.01-09-01003.1981 -
Neuroscience Oct 2019Most of Parkinson's disease (PD) patients experience gastrointestinal dysfunctions, including gastric hypomotility. The dorsal motor nucleus of the vagus (DMV) modulates...
Most of Parkinson's disease (PD) patients experience gastrointestinal dysfunctions, including gastric hypomotility. The dorsal motor nucleus of the vagus (DMV) modulates the motility of the upper gastrointestinal (GI) tract. Paraquat (P) administration induces Parkinsonism in experimental models, and we have developed recently an environmental model of Parkinsonism in which rats are treated with subthreshold doses of P and lectins (P + L), in both models rats develop reduced gastric motility prodromal to the full extent of motor deficits. The aim of the present study was to examine whether the membrane properties of DMV neurons in these two experimental models of Parkinsonism were altered. Whole cell recordings in slices containing DMV neurons were conducted in male Sprague Dawley rats which received either injections of paraquat (10 mg/kg i.p.; 10P), or oral administration of paraquat (1 mg/kg) and lectin (0.05% w/v; P + L). Morphological reconstructions of DMV neurons were conducted at the end of the recordings. The repolarization kinetics of the afterhyperpolarization phase of the action potential was accelerated in 10P neurons vs control, while the phase plot revealed a slower depolarizing slope. At baseline, the amplitude of miniature excitatory postsynaptic currents was increased in P + L neurons. No differences in the morphology of DMV neurons were observed. These data indicate that the membrane and synaptic properties of DMV neurons are altered in rodent models of Parkinsonism, in which neurons of 10P and P + L rats demonstrate an increased excitatory transmission, perhaps in an attempt to counteract the paraquat-induced gastric hypomotility.
Topics: Action Potentials; Animals; Excitatory Postsynaptic Potentials; Lectins; Male; Membranes; Models, Animal; Neurons; Paraquat; Parkinsonian Disorders; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Synapses; Vagus Nerve
PubMed: 31491501
DOI: 10.1016/j.neuroscience.2019.08.048 -
Alimentary Pharmacology & Therapeutics May 1999The application of 5-HT to the gut elicits a wide variety of effects because of the expression and wide distribution in the bowel of many subtypes of 5-HT. There is,... (Review)
Review
The application of 5-HT to the gut elicits a wide variety of effects because of the expression and wide distribution in the bowel of many subtypes of 5-HT. There is, however, no reason to believe that all of these receptors are stimulated by endogenous 5-HT. 5-HT has been found to be the neurotransmitter of a subset of myenteric interneurons, which evoke a slow excitatory postsynaptic response mediated by 5-HT1P receptors. The major enteric depot of 5-HT is found in mucosal enterochromaffin cells, which are sensory transducers that utilize 5-HT to activate both intrinsic (via 5-HT1P and 5-HT4 receptors) and extrinsic (via 5-HT3 receptors) primary afferent nerves. Mucosal 5-HT is inactivated by uptake into epithelial cells mediated by the same 5-HT transporter utilized by serotonergic neurons. Antagonism of 5-HT3 receptors by compounds such as alosetron should be useful in treating functional bowel disease because they can inhibit excitation of extrinsic sensory nerves by 5-HT without interfering with intrinsic enteric reflexes.
Topics: Animals; Carbolines; Colonic Diseases, Functional; Humans; Intestinal Mucosa; Intestines; Receptors, Serotonin; Serotonin; Serotonin Antagonists
PubMed: 10429737
DOI: No ID Found -
Journal de Physiologie 1991We have shown previously that dystrophin is a component of postsynaptic membranes in Torpedo electric organ and is localized at mammalian neuromuscular synapses. In...
We have shown previously that dystrophin is a component of postsynaptic membranes in Torpedo electric organ and is localized at mammalian neuromuscular synapses. In skeletal muscle, dystrophin is also detectable at the non-synaptic membrane of the myofiber, whereas in the electric organ, dystrophin is strictly localized to the postsynaptic membrane, and is not detectable in non-synaptic membranes. Multiple isoforms of dystrophin are present in skeletal muscle, and different isoforms could potentially be targetted to synaptic and non-synaptic membranes. We sought to determine whether the electric organ contains a single, or multiple isoforms of dystrophin, and we show here that the electric organ contains both a and b isoforms of dystrophin. Because dystrophin is found only at the postsynaptic membrane of the electric organ, we conclude that the two isoforms coexist in the postsynaptic membrane.
Topics: Animals; Dystrophin; Electric Organ; Synaptic Membranes; Torpedo
PubMed: 1818109
DOI: No ID Found -
Applied Biochemistry and Biotechnology Feb 1984A laminate model of the cleft-plus-postsynaptic membrane structure of the neuromuscular junction was studied. In order to prepare a model of the postsynaptic membrane,...
A laminate model of the cleft-plus-postsynaptic membrane structure of the neuromuscular junction was studied. In order to prepare a model of the postsynaptic membrane, the properties of acetylcholine (Ach) receptor-rich vesicles purified from Torpedo fish were measured. Immobilization of vesicles was demonstrated by various methods, in particular, by investigating collagen and carrageenan matrices as models of the fluid-filled fibrous matrix of the cleft. It was found that a laminated system employing a liquid membrane-containing vesicle suspension, together with a swollen collagen membrane, is an appropriate model for examining important transport/reception aspects of the cleft-plus-postsynaptic membrane structure. Combined transport with immobilization of Ach in the liquid membrane system was elucidated and effective diffusivities in the vesicle suspension layer were calculated. Effective diffusivities of the composite system simulating the cleft and the postsynaptic membrane were evaluated as well. These data illustrate the importance of penetrant immobilization in retarding the diffusion process during neurotransmission.
Topics: Acetylcholine; Animals; Biological Transport, Active; Carbachol; Collagen; Electric Organ; Kinetics; Membranes, Artificial; Models, Neurological; Neuromuscular Junction; Sodium; Synaptic Membranes; Torpedo
PubMed: 6476821
DOI: 10.1007/BF02798376 -
Journal of Neurocytology 2003Agrin is a heparan sulfate proteoglycan, which plays an essential role in the development and maintenance of the neuromuscular junction. Agrin is a stable component of... (Review)
Review
Agrin is a heparan sulfate proteoglycan, which plays an essential role in the development and maintenance of the neuromuscular junction. Agrin is a stable component of the synaptic basal lamina and strong evidence supports the hypothesis that agrin directs the formation of the postsynaptic apparatus, including aggregates of AChRs, and junctional folds. Changes in the distribution of agrin during synaptic remodeling, denervation and reinnervation reveal that agrin can be quickly and efficiently removed from the synaptic basal lamina in a regulated manner. In order to fully understand this mechanism we sought to identify those molecules that were responsible for the removal of agrin. Matrix Metalloproteinases (MMPs) were the most likely molecules since MMPs are involved in the regulation of the pericellular space, including the cleavage of matrix proteins. In particular, MMP3 has been shown to be effective in cleaving heparan sulfate proteoglycans. Antibodies to MMP3 recognize molecules concentrated in the extracellular matrix of perisynaptic Schwann cells. MMP3 specific phylogenic compounds reveal that active MMP3 is localized to the neuromuscular junction. Purified recombinant MMP3 can directly cleave agrin, and it can also remove agrin from synaptic basal lamina. MMP3 activity is itself regulated as activation of MMP3 is lost in denervated muscles. MMP3 null mutant mice have altered neuromuscular junction structure and function, with increased AChRs, junctional folds and agrin immunoreactivity. Altogether these results support the hypothesis that synaptic activity induces the activation of MMP3, and the activated MMP3 removes agrin from the synaptic basal lamina.
Topics: Action Potentials; Agrin; Animals; Basement Membrane; Humans; Matrix Metalloproteinase 3; Synapses
PubMed: 15034275
DOI: 10.1023/B:NEUR.0000020631.69804.f5 -
Frontiers in Molecular Neuroscience 2016Syntaxins are a family of membrane-integrated proteins that are instrumental in exocytosis of vesicles. Syntaxin-1 is an essential component of the presynaptic...
Syntaxins are a family of membrane-integrated proteins that are instrumental in exocytosis of vesicles. Syntaxin-1 is an essential component of the presynaptic exocytotic fusion machinery in the brain and interacts with several other proteins. Syntaxin-1 forms a four-helical bundle complex with proteins SNAP-25 and VAMP2 that drives fusion of vesicles with the plasma membrane in the active zone (AZ). Little is known, however, about the ultrastructural localization of syntaxin-1 at the synapse. We have analyzed the intrasynaptic expression of syntaxin-1 in glutamatergic hippocampal synapses in detail by using quantitative postembedding immunogold labeling. Syntaxin-1 was present in highest concentrations at the presynaptic AZ, supporting its role in transmitter release. Presynaptic plasma membrane lateral to the AZ, as well as presynaptic cytoplasmic (PreCy) vesicles were also labeled. However, syntaxin-1 was also significantly expressed in postsynaptic spines, where it was localized at the postsynaptic density (PSD), at postsynaptic lateral membranes and in postsynaptic cytoplasm. Postsynaptically, syntaxin-1 colocalized in the nanometer range with the N-methyl-D-aspartate (NMDA) receptor subunit NR2B, but only weakly with the AMPA receptor subunits GluA2/3. This observation points to the possibility that syntaxin-1 may be involved with NR2B vesicular trafficking from cytoplasmic stores to the postsynaptic plasma membrane, thus facilitating synaptic plasticity. Confocal immunofluorescence double labeling with PSD-95 and ultrastructural fractionation of synaptosomes also confirm localization of syntaxin-1 at the PSD.
PubMed: 26903802
DOI: 10.3389/fnmol.2016.00010