Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Presynaptic Terminals”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources
PubMed1997

Terminal morphology of two branches arising from a single stem-axon of pretectal (PSm) neurons in the common carp.

The induction of postsynaptic structures by presynaptic terminals is suggested in a teleost brain. Neurons in the nucleus pretectalis superficialis pars magnocellularis (PSm) in the common carp are known to send fibers to the corpus mamillare (CM) and the nucleus lateralis valvulae (NLV). Individual axons of PSm neurons bifurcate (or give off an axon collateral), both of which reach the target areas in the CM and NLV. The morphology of horseradish peroxidase-labeled terminals in the CM and NLV appears quite different in light microscopy. Terminals in the CM appear as a fine network of beaded (2-4 microns in diameter) fibers, while those in the NLV are larger (8-12 microns in transverse diameter) and cup-shaped, partially enveloping the soma of individual NLV neurons. In electron microscopy, however, these synapses in the CM and NLV share several ultrastructural similarities. Small (0.2 to 0.4-micron thick, 0.4 to 0.7-micron long) spine-like protrusions arising from dendrites in the CM, and from cell bodies in the NLV, invaginate into the axon terminals, and the synaptic junctions are always formed at the base of the protrusion in both areas. Development of this unusual morphology is inferred to be directed from the presynaptic side. The morphological similarity of the spine-like protrusions to the "spinule," which is thought to be formed in response to synaptic activation, is discussed.

Animals↗
PubMed2001

Presence of different ATP receptors on rat midbrain single synaptic terminals. Involvement of the P2X(3) subunits.

Adenosine 5'-triphosphate (ATP) stimulates a [Ca(2+)](i) increase via specific ionotropic receptors, termed P2X receptors, in rat midbrain presynaptic terminals. A microfluorimetric technique enabled study of the [Ca(2+)](i) increase in isolated single synaptic terminals, showing that 33.4+/-2.5% of them responded to ATP. Immunological studies carried out, after functional studies, with specific anti-P2X receptor subunit antibodies showed only positive labelling with anti-P2X(3) antibodies in 23.5+/-1.7% of the terminals. All positively P2X(3) labelled synaptic terminals responded to ATP. Nevertheless, not all of them responded to alpha,beta-meATP, these representing 6.7+/-1.5% of the total. In addition, 9.8+/-2.3% of the terminals responded to ATP but exhibit negative P2X(3)-labelling. These results demonstrate the existence of a heterogeneous population of ionotropic ATP receptors at the presynaptic level.

Animals↗
PubMed2001

Differential expression between synaptic vesicle proteins and presynaptic plasma membrane proteins in the anterior horn of amyotrophic lateral sclerosis.

This study concerns the immunohistochemical investigation of synaptic proteins in the anterior horn of amyotrophic lateral sclerosis (ALS). Antibodies against synapsin 1 and synaptophysin (i.e. synaptic vesicle proteins), and those against syntaxin and the synaptosomal-associated, 25 kDa protein, SNAP25 (i.e. presynaptic plasma membrane proteins) were used for immunostaining, respectively. Lumbar spinal cords from five ALS and eight control patients were examined. In the controls, all four synaptic proteins exhibited fine granular immunoreactivities, distributed throughout the spinal gray matter almost uniformly. In contrast, in all five ALS patients, two of the synaptic vesicle proteins examined decreased in the anterior horn neuropil diffusely, while in the same lumbar segments of these cases the immunoreactivities of the two presynaptic plasma membrane proteins showed no apparent decrease, or were only mildly diminished in the same gray matter area. These results indicate that, during the presynaptic terminal degeneration in the anterior horn of ALS, synaptic vesicle involvement may precede that of the presynaptic plasma membrane.

Adult↗
PubMed1999

A relationship between protein kinase C phosphorylation and calmodulin binding to the metabotropic glutamate receptor subtype 7.

Metabotropic glutamate receptor subtype 7 (mGluR7) is coupled to the inhibitory cyclic AMP cascade and is selectively activated by a glutamate analogue, L-2-amino-4-phosphonobutyrate. Among L-2-amino-4-phosphonobutyrate-sensitive mGluR subtypes, mGluR7 is highly concentrated at the presynaptic terminals and is thought to play an important role in modulation of glutamatergic synaptic transmission by presynaptic inhibition of glutamate release. To gain further insight into the intracellular signaling mechanisms of mGluR7, with the aid of glutathione S-transferase fusion affinity chromatography, we attempted to identify proteins that interact with the intracellular carboxyl terminus of mGluR7. Here, we report that calmodulin (CaM) directly binds to the carboxyl terminus of mGluR7 in a Ca(2+)-dependent manner. The CaM-binding domain is located immediately following the 7th transmembrane segment. We also show that the CaM-binding domain of mGluR7 is phosphorylated by protein kinase C (PKC). This phosphorylation is inhibited by the binding of Ca(2+)/CaM to the receptor. Conversely, the Ca(2+)/CaM binding is prevented by PKC phosphorylation. Collectively, these results suggest that mGluR7 serves to cross-link the cyclic AMP, Ca(2+), and PKC phosphorylation signal transduction cascades.

Amino Acid Sequence↗
PubMed2004

Axotomy-dependent and -independent synapse elimination in organ cultures of Wld(s) mutant mouse skeletal muscle.

Progressive "dying back" neurodegenerative diseases are debilitating due to loss of connectivity after nerve terminal and axonal withdrawal, which impairs peripheral nerve function and leads ultimately to neuronal cell death. The mutant mouse (Wallerian degeneration slow; Wld(s)) provides an accessible model system to understand orthograde and retrograde degeneration, because in these mice axotomy induces slow, progressive withdrawal of nerve terminals from motor endplates. Axon degeneration itself is about 10 times slower than in wild-type mice. We describe an organ culture paradigm that permits direct observation of the progressive changes in morphology of neuromuscular junctions in Wld(s) mutant mice. Normal nerve terminal and motor endplate morphology were maintained at most Wld(s) neuromuscular junctions for up to 72 hr in vitro. At others, synaptic boutons were removed from postsynaptic junctional folds in piecemeal fashion, as observed in adults in vivo. By contrast, nerve terminals degenerated rapidly and synchronously in wild-type muscle cultures, resembling Wallerian degeneration in vivo. These observations confirm that in Wld(s) mice, axotomy triggers a mechanism of nerve-terminal withdrawal that seems qualitatively different from that in wild-type animals. The piecemeal dismantling of presynaptic terminals resembles that occurring during neonatal synapse elimination. Organ cultures of neonatal Wld(s) muscle maintained for 1-2 days in vitro also showed no evidence of synaptic terminal degeneration, but elimination of polyneuronal innervation progressed in vitro at approximately the same rate as in vivo. Taken together, the data suggest that both natural and axotomy-induced forms of synapse withdrawal may be accessible to continuous observation and analysis, in organ-cultures of Wld(S) mouse muscles. This offers several advantages over repeated visualization of synaptic remodeling that has thus far been possible only in vivo.

Animals↗
PubMedDate not supplied

[Immunologic aspects of disorders of neuromuscular transmission. 2. Experimental autoimmune myasthenia gravis and the Lambert-Eaton myasthenic syndrome].

This paper describes two condition caused by disfunction of neuromuscular transport: experimental autoimmune myasthenia gravis (EAMG) and Lambert-Eaton myasthenic syndrome (LEMS). EAMG can be caused by immunization with acetylcholine receptors (AChR). As in myasthenia gravis, anti-AChR antibodies reduce the number of these receptors, which impedes normal neuromuscular transmission. LEMS patients have normal AChR function: however there is a disfunction of acetylcholine release from the presynaptic terminals. This is due to the formation of antibodies against the voltage gated calcium channels on the presynaptic nerve terminals.

Animals↗
PubMed1998

Calcium signals monitored from leopard frog optic tectum after the optic nerve has been selectively loaded with calcium sensitive dye.

We loaded adult leopard frog optic nerves with the calcium-sensitive dye Calcium Green-1 3000 mw dextran conjugate. The dye was transported to the optic tectum in approximately 6 days and selectively labeled optic nerve terminals as seen with confocal microscopy. Viewed with an intensified CCD system, electrical stimulation of the optic nerve in vitro increases Calcium Green-1 fluorescence significantly. With increasing number of pulses in pulse trains there was increased presynaptic facilitation as measured by increased fluorescence. Addition of nicotine to the bathing solution increased baseline fluorescence. These results suggest that Calcium Green-1 dextran conjugate can be actively transported in adult nerve fibers over a significant distance and is retained in presynaptic terminals in a form that allows monitoring of presynaptic calcium levels.

Animals↗
PubMed2002

Repolarization of the presynaptic action potential and short-term synaptic plasticity in the chick ciliary ganglion.

Stimulation-induced increases in synaptic efficacy have been described as being composed of multiple independent processes that arise from the activation of distinct mechanisms at the presynaptic terminal. In the chick ciliary ganglion, four components of short-term synaptic plasticity have been described: F1 and F2 components of facilitation, augmentation, and potentiation. In the present study, intracellular recording from the presynaptic calyciform nerve terminal of the chick ciliary ganglion revealed that the late repolarization and afterhypolarization (AHP) phases of the presynaptic action potential are affected by repetitive stimulation and that the time course of these effects parallel that of facilitation. The effects of these changes in the presynaptic action potential time course on calcium influx were tested by using the recorded action potential waveforms as voltage command stimuli during whole-cell patch-clamp recordings from acutely isolated chick ciliary ganglion neurons. The "facilitated" action potential waveform (slowed repolarization, decreased AHP amplitude) evoked calcium current with slightly but significantly greater total calcium influx. Taken together, these results are consistent with the hypothesis that activity-dependent changes in the presynaptic action potential are one of several mechanisms contributing to the facilitation phase of stimulation-induced increases in transmitter release in this preparation.

Action Potentials↗
PubMed2006

Entering neurons: botulinum toxins and synaptic vesicle recycling.

Botulinum toxins are metalloproteases that act inside nerve terminals and block neurotransmitter release through their cleavage of components of the exocytosis machinery. These toxins are used to treat human diseases that are characterized by hyperfunction of cholinergic terminals. Recently, evidence has accumulated that gangliosides and synaptic vesicle proteins cooperate to mediate toxin binding to the presynaptic terminal. The differential distribution of synaptic vesicle protein receptors, gangliosides and toxin substrates in distinct neuronal populations opens up the possibility of using different serotypes of botulinum toxins for the treatment of central nervous system diseases caused by altered activity of selected neuronal populations.

Animals↗
PubMed2006

Estimate of the chloride concentration in a central glutamatergic terminal: a gramicidin perforated-patch study on the calyx of Held.

The function of presynaptic terminals is regulated by intracellular Cl-, the levels of which modify vesicular endocytosis and transmitter refilling and mediate the effects of presynaptic ligand-gated Cl- channels. Nevertheless, the concentration of Cl- in a central nerve terminal is unknown, and it is unclear whether terminals can regulate Cl- independently of the soma. Using perforated-patch recording in a mammalian synapse, we found that terminals accumulate Cl- up to 21 mm, between four and five times higher than in their parent cell bodies. Changing [Cl-] did not alter vesicular glutamate content in intact terminals, unlike in vitro experiments. Thus, glutamatergic terminals maintain an elevated Cl- concentration without compromising synaptic transmission.

Action Potentials↗
PubMed2004

Striatal monoamine terminals in Lewy body dementia and Alzheimer's disease.

We used positron emission tomography (PET) with (+)-[(11)C]dihydrotetrabenazine ([+]-[(11)C]DTBZ) to examine striatal monoaminergic presynaptic terminal density in 20 patients with dementia with Lewy bodies (DLB), 25 with Alzheimer's disease (AD), and 19 normal elderly controls. Six DLB patients developed parkinsonism at least 1 year before dementia (DLB/PD) and 14 developed dementia before parkinsonism or at about the same time (DLB/AD). Striatal mean binding potential was decreased by 62 to 77% in the DLB/PD group and 45 to 67% in the DLB/AD compared to AD and control. Binding was lower in the DLB/PD group than the DLB/AD, but the differences reached only marginal significance in the caudate nucleus. No differences were found between AD and control groups though a few AD patients had binding values below the range of the controls. Subsequent neuropathological examination in one AD patient revealed both AD and DLB changes despite the absence of clinical parkinsonism. Both DLB groups had an anterior to posterior binding deficit gradient relative to controls, largest in posterior putamen, smaller in anterior putamen, smallest in caudate nucleus. The DLB/AD group showed significant binding asymmetry only in posterior putamen. We conclude that PET with (+)-[(11)C]DTBZ differentiates DLB from AD, and decreased binding in AD may indicate subclinical DLB pathology in addition to AD pathology.

Aged↗
PubMed2000

Presynaptic calcium stores underlie large-amplitude miniature IPSCs and spontaneous calcium transients.

The cellular mechanisms responsible for large miniature currents in some brain synapses remain undefined. In Purkinje cells, we found that large-amplitude miniature inhibitory postsynaptic currents (mIPSCs) were inhibited by ryanodine or by long-term removal of extracellular Ca2+. Two-photon Ca2+ imaging revealed random, ryanodine-sensitive intracellular Ca2+ transients, spatially constrained at putative presynaptic terminals. At high concentration, ryanodine decreased action-potential-evoked rises in intracellular Ca2+. Immuno-localization showed ryanodine receptors in these terminals. Our data suggest that large mIPSCs are multivesicular events regulated by Ca2+ release from ryanodine-sensitive presynaptic Ca2+ stores.

Animals↗
PubMed2000

Presynaptic Ca(2+) influx at a mouse central synapse with Ca(2+) channel subunit mutations.

Genetic alterations in Ca(2+) channel subunits can be used to study the interaction among channel subunits and their roles in channel function. P/Q- and N-type Ca(2+) channels reside at the presynaptic terminal and control the release of neurotransmitter at mammalian central synapses. We used fluorescence imaging techniques to investigate presynaptic Ca(2+) currents and neurotransmitter release at hippocampal Schaffer collateral synapses in both tottering (tg, alpha(1A) subunit) and lethargic (lh, beta(4) subunit) mutant mice. Application of selective toxins revealed a large reduction in presynaptic P/Q-type Ca(2+) transients, from 39% of total in +/+ mice to 6% in tg/tg mice, whereas the proportion of N-type increased from 35 to 68%, respectively. Neurotransmitter release in the tg/tg mutant relied almost exclusively on N-type channels, as shown by the complete blockade of synaptic transmission with omega-conotoxin GVIA. Remarkably, loss of beta4, a subunit predicted to regulate the subcellular targeting and modulation of both P/Q- and N-type channels, resulted in no significant difference in the ratio of Ca(2+) channel subtypes or Ca(2+) dependence of neurotransmitter release in lethargic mice. G-protein-mediated inhibition of Ca(2+) channels was also unaltered. These results indicate that a profound decrease in presynaptic P/Q-type currents leads to dependence of neurotransmitter release on N-type channels. In contrast, absence of beta(4) appears not to compromise either P/Q- or N-type channel function at this hippocampal synapse, implicating rescue of presynaptic Ca(2+) currents by other available beta subunits. The present study reveals compensatory molecular mechanisms in the regulation of presynaptic Ca(2+) entry and neurotransmitter release.

2-Amino-5-phosphonovalerate↗
PubMed1994

Ultrastructural evidence for synaptic inputs of enkephalinergic nerve terminals to target neurons in the rat arcuate nucleus.

The morphological support of interactions between enkephalins and three systems--beta-endorphin (beta-END), tyrosine hydroxylase (TH), or neuropeptide Y (NPY)--well represented in the arcuate nucleus, was examined by using an electron microscopic double immunostaining combining two sensitive chromogens, diaminobenzidine (DAB) and tetramethylbenzidine (TMB). The first step consisted of visualizing Metenkephalinergic terminals with DAB reaction product, and the second one involved detecting the antigens TH, beta-END, and NPY in their respective neurons with TMB reaction product. Ultrastructural analysis revealed enkephalinergic terminals presynaptic to TH-immunopositive cells and dendrites, principally in the dorsal portion of the arcuate nucleus. Enkephalinergic nerve terminals also contacted synaptically ventrolaterally located beta-END-immunoreactive cells. In the ventromedial arcuate nucleus, few synaptic contacts were observed between enkephalinergic boutons and NPY neurons, which were principally in close apposition with glial processes. Enkephalin-immunoreactive synapses were more frequently seen on TH-immunopositive neurons. This TH neuronal group is known to correspond to the dopaminergic tuberoinfundibular neurons implicated in the control of reproductive functions. The pattern of distribution of the different synapses within the arcuate nucleus (TH dorsal, beta-END ventrolaterally; NPY ventromedially) suggests that enkephalins may play a role in the neuroendocrine regulation of gonadotropin and prolactin secretion. The results provide evidence that enkephalins, in the arcuate nucleus, exert a postsynaptic action on the beta-END cells in addition to the presynaptic regulation previously demonstrated in the mediobasal hypothalamus, related to beta-END release. Moreover, the arcuate nucleus is a site of intercellular relationships between enkephalins and dopamine and between enkephalins and other peptides such as NPY.

3,3'-Diaminobenzidine↗
PubMed1991

Role of residual calcium in synaptic depression and posttetanic potentiation: fast and slow calcium signaling in nerve terminals.

Trains of action potentials evoked rises in presynaptic Ca2+ concentration ([Ca2+]i) at the squid giant synapse. These increases in [Ca2+]i were spatially nonuniform during the trains, but rapidly equilibrated after the trains and slowly declined over hundreds of seconds. The trains also elicited synaptic depression and augmentation, both of which developed during stimulation and declined within a few seconds afterward. Microinjection of the Ca2+ buffer EGTA into presynaptic terminals had no effect on transmitter release or synaptic depression. However, EGTA injection effectively blocked both the persistent Ca2+ signals and augmentation. These results suggest that transmitter release is triggered by a large, brief, and sharply localized rise in [Ca2+]i, while augmentation is produced by a smaller, slower, and more diffuse rise in [Ca2+]i.

Action Potentials↗
PubMed1985

A calcium-activated potassium current in motor nerve terminals of the mouse.

Local circuit currents involving presynaptic terminals were recorded by micro-electrodes inserted into the perineurium of nerves from the triangularis sterni muscle of the mouse. A transient outward current component was isolated by blocking the voltage-activated (delayed rectifier) K current by 3,4-diaminopyridine (3,4-DAP). The amplitude of this component depended on external K concentration and fell to zero at [K]o = 15 mM. Since it also depended on [Ca]o, it was identified as a Ca-activated K current (IK(Ca)). Tetraethylammonium (TEA) (2 mM), Ba (2 mM), Co (10 mM) and Mn (2.5 mM) blocked IK(Ca). IK(Ca) decayed to zero in approximately 12 ms and recovered from inactivation in about 100 ms. Ca current was enhanced in inverse proportion to the degree of IK(Ca) depression. The possible role of IK(Ca) in the process of neuromuscular facilitation is briefly discussed.

4-Aminopyridine↗
PubMed1995

Presynaptic proteins involved in exocytosis in Drosophila melanogaster: a genetic analysis.

Neuronal communication involves the fusion of neurotransmitter filled synaptic vesicles with the presynaptic terminal. This exocytotic event depends upon proteins present in three separate compartments: the synaptic vesicle, the synaptic cytosol, and the presynaptic membrane. Recent data indicate that the basic components of exocytotic pathways, including those used for neurotransmitter release, are conserved from yeast to human. Genetic dissection of the secretory pathway in yeast, identification of the target proteins cleaved by the clostridial neurotoxins and biochemical characterization of the interactions of synaptic proteins from vertebrates have converged to provide the SNARE (soluble NSF attachment protein receptor) hypothesis for vesicle trafficking. This model proposes that proteins present in the vesicle (v-SNAREs) interact with membrane receptors (t-SNAREs) to provide a molecular scaffold for cytosolic proteins involved in fusion. The hypothesis that these mechanisms function at the synapse relies largely upon in vitro evidence. Recently, genetic approaches in mice, C. elegans and the fruitfly, Drosophila melanogaster, have been used to dissect the in vivo function of numerous proteins involved in synaptic transmission. This review covers recent progress and insights provided by a genetic dissection of neurotransmitter release in Drosophila. In addition, we will provide evidence that the mechanisms for synaptic communication are highly conserved from invertebrates to vertebrates, making Drosophila an ideal model system to further unravel the intricacies of synaptic transmission.

Animals↗
PubMed2004

Localization of brain-derived neurotrophic factor to distinct terminals of mossy fiber axons implies regulation of both excitation and feedforward inhibition of CA3 pyramidal cells.

Hippocampal dentate granule cells directly excite and indirectly inhibit CA3 pyramidal cells via distinct presynaptic terminal specializations of their mossy fiber axons. This mossy fiber pathway contains the highest concentration of brain-derived neurotrophic factor (BDNF) in the CNS, yet whether BDNF is positioned to regulate the excitatory and/or inhibitory pathways is unknown. To localize BDNF, confocal microscopy of green fluorescent protein transgenic mice was combined with BDNF immunohistochemistry. Approximately half of presynaptic granule cell-CA3 pyramidal cell contacts were found to contain BDNF. Moreover, enhanced neuronal activity virtually doubled the percentage of BDNF-immunoreactive terminals contacting CA3 pyramidal cells. To our surprise, BDNF was also found in mossy fiber terminals contacting inhibitory neurons. These studies demonstrate that mossy fiber BDNF is poised to regulate both direct excitatory and indirect feedforward inhibitory inputs to CA3 pyramdal cells and reveal that seizure activity increases the pool of BDNF-expressing granule cell presynaptic terminals contacting CA3 pyramidal cells.

Animals↗