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Results for “Presynaptic Terminals”

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At least 127 records · Page 7Linked to original sources
PubMed1999

Cooperative Ca2+ removal from presynaptic terminals of the spiny lobster neuromuscular junction.

Stimulation-induced changes in presynaptic free calcium concentration ([Ca2+]i) were examined by fluorescent imaging at the spiny lobster excitor motor nerve terminals. The Ca2+ removal process in the terminal was analyzed based on a single compartment model, under the assumption that the Ca2+ removal rate from the terminal cytoplasm is proportional to nth power of [Ca2+]i. During 100 nerve stimuli at 10-100 Hz, [Ca2+]i reached a plateau that increased in a less-than-linear way with stimulation frequency, and the power index, n, was about 2. In the decay time course after stimulation, n changed with the number of stimuli from about 1.4 after 10 stimuli to about 2 after 100 stimuli. With the change of n from 1.4 to 2, the rate became larger at high [Ca2+]i (>1.5 microM), but was smaller at low [Ca2+]i (<1 microM). These results suggest that a cooperative Ca2+ removal mechanism of n = 2, such as mitochondria, may play an important role in the terminal. This view is supported by the gradual increase in the [Ca2+]i plateau during long-term stimulation at 20-50 Hz for 60 s and by the existence of a very slow [Ca2+]i recovery process after this stimulation, both of which may be due to accumulation of Ca2+ in the organelle.

Animals↗
PubMed1994

GTP-binding proteins: necessary components of the presynaptic terminal for synaptic transmission and its modulation.

Using synapses that form between somata of Helisoma neurons in cell culture, we have studied the presynaptic regulation of synaptic transmission. Guanosine 5'-triphosphate (GTP)-binding proteins play critical roles in regulating synaptic transmission. Injection of guanine nucleotide analogues has demonstrated that one or more GTP-binding protein is necessary for transmitter release. Heterotrimeric G proteins continuously regulate the amount of transmitter released at the synapse by modulating potassium and calcium channels, and by controlling the secretory response to calcium. Perturbations of the synapse using guanosine 5'-diphosphate (GDP) beta S, GTP gamma S, and rab effector domain peptides suggest that small GTP-binding proteins also play critical roles in the synapse. We discuss the possibility that rab3, or related proteins, are required for exocytosis, and by cooperating with other proteins maintain vesicles in a docked state in the synapse.

Animals↗
PubMed1966

On the permeability of the presynaptic terminal of the crayfish neuromuscular junction during synaptic inhibition and the action of gamma-aminobutyric acid.

1. The contribution of chloride to presynaptic inhibition of the crayfish neuromuscular junction during the action of gamma-aminobutyric acid (GABA) and the inhibitory transmitter was investigated. Chloride in van Harreveld's solution was replaced with propionate, acetate, methylsulphate or glycerophosphate and electrical changes were recorded intracellularly and extracellularly with micro-electrodes.2. When the preparation was soaked in Cl-deficient solutions, the quantum content of the excitatory junctional potentials (e.j.p.s), calculated from the number of failures, was increased.3. The presynaptic inhibitory action of GABA was reduced or almost absent when the preparation was soaked in Cl-deficient solution. In Cl-deficient solution the stimulation of the inhibitory axon showed little or no inhibitory action on e.j.p.s.4. If GABA was applied shortly after the outside solution was changed to the Cl-deficient one, the frequency of the spontaneous e.j.p.s was increased transiently.5. It is suggested that GABA or the inhibitory transmitter act on the presynaptic excitatory terminal and predominantly increase its permeability to chloride.

Journal Article↗
PubMed2003

Activation of presynaptic glycine receptors facilitates glycine release from presynaptic terminals synapsing onto rat spinal sacral dorsal commissural nucleus neurons.

Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Here we report the novel finding that presynaptic glycine autoreceptors modulate release from terminals synapsing onto rat spinal sacral dorsal commissural nucleus (SDCN) neurons. In mechanically dissociated SDCN neurons, in which functional presynaptic nerve terminals remain adherent to the isolated neurons, exogenously applied glycine (3 microM) increased the frequency of glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs) without affecting their amplitudes or decay times. This suggests that glycine acts presynaptically to increase glycine release probability. Picrotoxin, at a concentration that had little direct effect on sIPSC frequency and amplitude (30 microM), significantly attenuated glycine-induced presynaptic sIPSC facilitation. The glycine-induced sIPSC frequency facilitation was completely abolished either in a Ca(2+)-free external solution or in the presence of 100 microM Cd2+, suggesting the involvement of extracellular Ca2+ influx into the nerve terminals. The glycine action was also completely occluded in the presence of 300 nM tetrodotoxin. In recordings from SDCN neurons in spinal cord slices, glycine (10 microM) increased evoked IPSC (eIPSC) amplitude and decreased the extent of paired-pulse facilitation. In response to brief high frequency stimulus trains the eIPSCs displayed a profound frequency-dependent facilitation that was greatly reduced by picrotoxin (30 microM). These results indicate that glycine acts at presynaptic autoreceptors, causing depolarization of the glycinergic nerve terminals, the subsequent activation of voltage-dependent Na+ and Ca2+ channels, and facilitation of glycine release. Furthermore, this presynaptic facilitation was observed under more physiological conditions, suggesting that these glycinergic autoreceptors may contribute to the integration of local inhibitory inputs to SDCN neurons.

Algorithms↗
PubMed1997

Interplay between sodium and calcium dynamics in granule cell presynaptic terminals.

Fluorescent indicators were used to detect stimulus-evoked changes in presynaptic levels of intracellular sodium (Na(i)) and calcium (Ca(i)) in granule cell parallel fibers in brain slices from rat cerebellum. Ca(i) increased during stimulation, and three exponentials were needed to approximate its return to prestimulus levels. Ca(i) decayed to approximately 10% of peak levels with tau approximately 100 ms, to approximately 1% of peak values with tau approximately 6 s, and then returned to prestimulus levels with tau approximately 1-2 min. After stimulation, Na(i) accumulated in two phases; one rapid, the other continuing for several hundred milliseconds. The return of Na(i) to prestimulus levels was well approximated by a double exponential decay with time constants of 6-17 s and 2-3 min. Manipulations that prevented calcium entry eliminated both the slow component of sodium entry and the rapid component of Na(i) decay. Reductions of extracellular sodium slowed the rapid phase of Ca(i) decay. These Ca(i) and Na(i) transients were well described by a model in which the plasma membrane of presynaptic boutons contained both a sodium/calcium exchanger and a calcium ATPase (Ca-ATPase). According to this model, immediately after stimulation the sodium/calcium exchanger removes calcium from the terminal more rapidly than does the Ca-ATPase. Eventually, the large concomitant sodium influx brings the exchanger into steady-state, leaving only the Ca-ATPase to remove calcium. This perturbs the equilibrium of the sodium/calcium exchanger, which opposes the Ca-ATPase, leading to a slow return of Ca(i) and Na(i) to resting levels.

Animals↗
PubMed1996

Injury-induced remodelling and regeneration of the ribbon presynaptic terminal in vitro.

The neuronal response to axonal injury may relate to the type of insult incurred. Recently, neuritic and presynaptic varicosity regeneration by isolated adult salamander photoreceptors was demonstrated. We have used this system to compare the rod photoreceptor response to two types of injury: denervation/detargeting, the removal of pre- and postsynaptic partners from the axon terminal, and axotomy, the removal of the axon terminal itself. Cells were followed with time-lapse video microscopy for 24-48 h in culture and immunolabelled for SV2 or synaptophysin to identify synaptic vesicle-containing varicosities. Although all injured cells responded with regenerative growth, denervated/detargeted photoreceptors (i.e. neurons which retain their axon terminal) grew 80% more processes and fourfold more presynaptic varicosities than axotomized neurons. In cells which retained their original axon and terminal, varicosity formation generally began with axon retraction. Retraction was followed by elaboration of a lamellipodium and, by 48 h, development of varicosity-bearing neurites from the lamellipodium. Synaptic vesicle protein localization in denervated/detargeted cells paralleled axon terminal reorganization. Axotomized cells, in contrast, lacked synaptic vesicle protein immunoreactivity during this period. To detect synaptic protein synthesis, photoreceptors were examined for colocalization of synaptic vesicle protein with rab6, a Golgi marker, by confocal microscopy. As expected, synaptic vesicle protein staining was present in the Golgi complex during regeneration; however, in cells with an axon, new synaptic vesicle protein-labelled varicosities were found at early stages, prior to the appearance of immunolabel in the Golgi complex. The data demonstrate remarkable plasticity in the ribbon synapse, and suggest that in adult rod cells with an intact axon terminal, synaptic vesicle protein synthesis is not a prerequisite for the formation of new presynaptic-like terminals. We propose that preexisting axonal components are reutilized to expedite presynaptic renewal as an early response to denervation/detargeting.

Ambystoma↗
PubMed2005

Presynaptic GABAA receptors facilitate spontaneous glutamate release from presynaptic terminals on mechanically dissociated rat CA3 pyramidal neurons.

Mossy fiber-derived giant spontaneous miniature excitatory postsynaptic currents have been suggested to be large enough to generate action potentials in postsynaptic CA3 pyramidal neurons. Here we report on the functional roles of presynaptic GABA(A) receptors on excitatory terminals in contributing to spontaneous glutamatergic transmission to CA3 neurons. In mechanically dissociated rat hippocampal CA3 neurons with adherent presynaptic nerve terminals, spontaneous excitatory postsynaptic currents were recorded using conventional whole-cell patch clamp recordings. In most recordings, unusually large spontaneous excitatory postsynaptic currents up to 500 pA were observed. These large spontaneous excitatory postsynaptic currents were highly sensitive to group II metabotropic glutamate receptor activation, and were still observed even after the blockade of voltage-dependent Na(+) or Ca(2+) channels. Exogenously applied muscimol (0.1-3 microM) significantly increased the frequency of spontaneous excitatory postsynaptic currents including the large ones. This facilitatory effect of muscimol was completely inhibited in the presence of 10 microM 6-imino-3-(4-methoxyphenyl)-1(6H)-pyridazinebutanoic acid HBr, a specific GABA(A) receptor antagonist. Pharmacological data suggest that activation of presynaptic GABA(A) receptors directly depolarizes glutamatergic terminals resulting in the facilitation of spontaneous glutamate release. In the current-clamp condition, a subset of large spontaneous excitatory postsynaptic potentials triggered action potentials, and muscimol greatly increased the frequency of spontaneous excitatory postsynaptic potential-triggered action potentials in postsynaptic CA3 pyramidal neurons. The results suggest that presynaptic GABA(A) receptors on glutamatergic terminals play an important role in the excitability of CA3 neurons as well as in the presynaptic modulation of glutamatergic transmission onto hippocampal CA3 neurons.

Action Potentials↗
PubMed2005

Strong effects of subphysiological temperature on the function and plasticity of mammalian presynaptic terminals.

Most cellular processes are known to be strongly temperature dependent. Nevertheless, a large fraction of studies of mammalian synaptic function have been and are performed near room temperature (i.e., at least 10 degrees C below physiological temperature). Here, we examined the effects of temperature on presynaptic function in primary cultures of rat hippocampal neurons. FM dyes, VAMP (vesicle-associated membrane protein)-GFP (green fluorescent protein) transfection, and HRP uptake were used to quantify various aspects of synaptic vesicle recycling. Our results show that there are very substantial differences in synaptic vesicle recycling at physiological temperature as opposed to the common, lower experimental temperatures. At 37 degrees C, compared with 23 degrees C, the speed of both exocytosis and endocytosis was higher. The size of the recycling vesicle pool (in both number of vesicles and spatial extent) was twofold larger at 37 degrees C. In addition, although repeated 10 Hz electrical stimulation caused an NMDA receptor-dependent enlargement (averaging 170%) of the measurable recycling vesicle pool at 23 degrees C, the same stimulus repetition had no effect at 37 degrees C. These results show that it is potentially misleading to extend conclusions drawn about vesicle function or presynaptic plasticity at lowered experimental temperature to physiological conditions and that much new experimental work at the higher physiological temperature range will be needed to understand the true parameters of presynaptic functions.

Animals↗
PubMed1999

Occlusive responses to adenosine A1 receptor and muscarinic M2 receptor activation on hippocampal presynaptic terminals.

There is substantial evidence for an interaction between adenosine A1 and muscarinic M1/M3 receptors in some tissues, either at the level of the receptors themselves or at the associated transduction system. We have now addressed the question of whether there is a similar interaction between A1 and presynaptic M2 receptors in the hippocampus. The effects of cyclopentyladenosine (CPA) were studied alone or in combination with the M2 receptor agonist oxotremorine-M. The ability of both to depress synaptic transmission presynaptically at the concentrations used was confirmed using paired-pulse inhibition. When combined at a range of concentrations, the effects of the two agents were less than additive, suggesting that they are acting by a common transduction system. The results indicate that the modulatory, antagonistic effects of A1 adenosine receptors are exerted not only on postjunctional M1/M3 receptors but also at M2 presynaptic receptors.

Adenosine↗
PubMed2004

Functional compensation of P/Q by N-type channels blocks short-term plasticity at the calyx of Held presynaptic terminal.

Calcium channels of the P/Q subtype mediate transmitter release at the neuromuscular junction and at many central synapses, such as the calyx of Held. Transgenic mice in which alpha1A channels are ablated provide a powerful tool with which to test compensatory mechanisms at the synapse and to explore mechanisms of presynaptic regulation associated with expression of P/Q channels. Using the calyx of Held preparation from the knock-out (KO) mice, we show here that N-type channels functionally compensate for the absence of P/Q subunits at the calyx and evoke giant synaptic currents [approximately two-thirds of the magnitude of wild-type (WT) responses]. However, although evoked paired-pulse facilitation is prominent in WT, this facilitation is greatly diminished in the KO. In addition, direct recording of presynaptic calcium currents revealed that the major functional difference was the absence of calcium-dependent facilitation at the calyx in the P/Q KO animals. We conclude that one physiological function of P/Q channels is to provide additional facilitatory drive, so contributing to maintenance of transmission as vesicles are depleted during high throughput synaptic transmission.

Animals↗
PubMed2004

Action potential-evoked and ryanodine-sensitive spontaneous Ca2+ transients at the presynaptic terminal of a developing CNS inhibitory synapse.

The existence of spontaneous calcium transients (SCaTs) dependent on intracellular store activation has been reported in putative axonal terminals of cerebellar basket interneurons. We used the two-photon imaging technique to optically identify basket terminals in acute cerebellar slices of young rats (11-16 d old) and study the properties of SCaTs unambiguously localized in these regions. The whole-cell recording configuration and preloading technique were alternatively used to load the calcium-dependent dye in the interneuron and compare SCaTs with action potential evoked calcium transients. SCaTs were observed in the basket terminals at frequencies that were significantly increased after bath application of 10 microm ryanodine and did not depend on P/Q- or N-type voltage-dependent calcium channel activation. They originated at specific sites where bursts of events with temporal separation as small as 200 msec could be generated. Their sites of origin were spaced on average 6 microm apart and were preferentially located near axonal endings. SCaTs had amplitudes comparable with those of Ca2+ rises evoked by single action potentials that lead to release of neurotransmitter, as confirmed by parallel recordings of preloaded terminals and evoked IPSCs in the postsynaptic Purkinje cells. These results support the hypothesis that SCaTs at basket terminals underlie the large miniature IPSCs characteristic of Purkinje cells.

Action Potentials↗
PubMed2003

Neurexin mediates the assembly of presynaptic terminals.

Neurexins are a large family of proteins that act as neuronal cell-surface receptors. The function and localization of the various neurexins, however, have not yet been clarified. Beta-neurexins are candidate receptors for neuroligin-1, a postsynaptic membrane protein that can trigger synapse formation at axon contacts. Here we report that neurexins are concentrated at synapses and that purified neuroligin is sufficient to cluster neurexin and to induce presynaptic differentiation. Oligomerization of neuroligin is required for its function, and we find that beta-neurexin clustering is sufficient to trigger the recruitment of synaptic vesicles through interactions that require the cytoplasmic domain of neurexin. We propose a two-step model in which postsynaptic neuroligin multimers initially cluster axonal neurexins. In response to this clustering, neurexins nucleate the assembly of a cytoplasmic scaffold to which the exocytotic apparatus is recruited.

Alanine↗
PubMed2001

Neurotrophins act at presynaptic terminals to activate synapses among cultured hippocampal neurons.

We have recently demonstrated that embryonic E16 hippocampal neurons grown in cultures are unable to form fast synaptic connections unless treated with BDNF or NT-3. This experimental system offers an opportunity to define the roles of neurotrophins in processes leading to formation of functional synaptic connections. We have used ultrastructural and electrophysiological methods to explore the cellular locations underlying neurotrophin action on synaptic maturation. The rate of spontaneous miniature excitatory postsynaptic currents (mEPSCs) evoked by hyperosmotic stimulation was 7-16-fold higher in neurotrophin-treated cells than in controls. In addition, the potent neurotransmitter-releasing drug alpha-latrotoxin was virtually ineffective in the control cells while it stimulated synaptic events in neurotrophin-treated cells. Likewise, the membrane-bound dye FM1-43 was taken up by terminals in neurotrophin-treated cultures five-fold more than in controls. Both the total number and the number of docked synaptic vesicles were increased by neurotrophin treatment. Activation of synaptic responses by neurotrophins occurred even when postsynaptic glutamate receptors and action potential discharges were pharmacologically blocked. These results are consistent with a presynaptic locus of action of neurotrophins to increase synaptic vesicle density which is critical for rapid synaptic transmission. They also suggest that neurotrophins can activate synapses in the absence of pre- and postsynaptic neuronal activity.

2-Amino-5-phosphonovalerate↗