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 1,711 records · Page 95Linked to original sources
PubMed1997

Antagonism of mGlu receptors and potentiation of EPSCs at rat spinal motoneurones in vitro.

The patch-clamp technique has been used to record synaptic responses, elicited by electrical stimulation of dorsal roots, in 28 single motoneurones of in vitro spinal cord preparations from neonate (P5 to P8) rats. The effects of (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) (200 microM), a potent antagonist at L-2-amino-4-phosphonobutanoate (AP4)-sensitive receptors, and (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) (500 microM), which is a less selective antagonist of mGluRs, were tested on EPSCs alone and as antagonists of AP4-induced depression of EPSCs. The EC50 for depression of EPSCs by AP4 (1.16 +/- 0.12 microM, n = 8) was increased to 18.9 +/- 0.7 microM (n = 6) by MPPG. MCPG (500 microM) had no significant effect on the depressant potency of AP4. Under control conditions, EPSCs had mean peak amplitudes of 983 pA +/- 64 SEM and mean charge transferred of 306 +/- 37 pC (n = 28). These values were increased significantly (p < 0.05) to 1168 +/- 68 pA and 363 +/- 39 pC by MPPG (n = 6), and 1150 +/- 54 pA and 358 +/- 33 pC (n = 6) by MCPG. There was no significant difference between the enhancement of the initial peak of the EPSCs (mean latency from stimulus artifact 5.9 +/- 0.3 ms) and later components, suggesting mGluRs to be present on primary afferent terminals presynaptic to motoneurones as well as in pathways via interneurones. These results are consistent with the presence of at least two types of presynaptic mGluR that modulate release of glutamate in segmental pathways convergent onto motoneurones. These receptors appear to be activated by interstitial glutamate tonically present in the present preparations.

Animals↗
PubMed1998

Modifications in brain cAMP- and calcium/calmodulin-dependent protein kinases induced by treatment with S-adenosylmethionine.

Several lines of evidence suggest that the mechanism of action of antidepressant drugs (AD) involves adaptive changes occurring in intraneuronal post-receptor signal transduction cascades. Protein phosphorylation has a key role in signal transduction and was previously found to be a target in the action of AD (5-HT and/or NA reuptake blockers). Several studies showed that cAMP- and type II Ca2+/calmodulin-dependent protein kinases (PKA and CaMKII) are markedly affected by typical AD in two different and complementary cellular districts, respectively microtubules (a somatodendritic compartment) and synaptic vesicles (a presynaptic terminal compartment). In order to investigate whether the effect on protein kinases may be involved in the therapeutic action of drugs it is interesting to compare the effect of atypical AD with that of typical drugs. In this study the effect of the atypical AD S-adenosylmethionine (SAMe) was tested. Repeated (12 days) SAMe treatment induced in cerebrocortical microtubules an increase in the binding of cAMP to the RII PKA regulatory subunit and an increase in the endogenous phosphorylation of microtubule-associated protein 2, an effect resembling that of typical AD. In synaptic terminals the treatment induced an increase in the activity of CaMKII and in the endogenous phosphorylation of vesicular substrates. However, this modification was found in the cerebral cortex rather than in the hippocampus, where typical AD affect CaMKII. In addition the synapsin I level was decreased in the hippocampus and increased in the cerebral cortex, an effect not detected with typical AD.

Animals↗
PubMed1975

Pathologic axons and synapses in human neuropsychiatric disorders.

Ultrastructural studies of cerebral biopsy specimens from patients with various forms of psychomotor retardation and dementia have disclosed pathologic changes in axons and presynaptic or postsynaptic processes. The clinical disorders with lesions in axons and presynaptic terminals are reviewed. Three basic abnormalities have been detected: proliferation of tubulovesicular structures which probably originate from the smooth endoplasmic reticulum, "abnormal" mitochondria, and proliferation of 80 to 100 A filaments. Understanding of the pathogenesis of human disorders associated with axonic or "synaptic" lesions will probably depend on progress in areas of basic biomedical research concerned with the synthesis and turnover of biological membranes and the packaging and secretion of neurotransmitters, elucidation of mechanisms of cytoplasmic streaming and axoplasmic flow, and biophysical and biochemical characteristics and functions of "fibrous" proteins (neurotubules, neurofilaments, pathologic fibrous proteins). In several cases of mental retardation of unknown etiology, abnormal dendritic spines of cortical neurons have been observed with the use of the Golgi method. These dendritic (postsynaptic) disorders have been attributed to defective development ("dysgenesis"). The knowledge provided by ultrastructural analysis of brain tissue from the human disorders of mental retardation or dementia is "still formless, incomplete, lacking the essential threads of connection," and only future developments in lacking neurobiology will make possible the dissection of the primary phenomena from the secretory and probably irrelevant findings.

Animals↗
PubMed1993

Biochemical correlates of long-term potentiation in hippocampal synapses.

Figure 2 summarizes biochemical events which are currently known or hypothesized to participate in LTP induction/maintenance. Current evidence strongly suggests that postsynaptic Ca2+, both entered from the outside of cells and released from intracellular stores, is the initial key substance for the induction of LTP. A rise of [Ca2+]i triggers a variety of enzymatic reactions and initiates the enhancement of synaptic transmission. This first step may be achieved by direct/indirect phosphorylations of protein molecules in postsynaptic receptors/ion channels. This would result in an increase in receptor sensitivity. An immediate increase in the number of available postsynaptic receptors by modifications of spine morphology is another candidate. Such modifications may be accomplished by cytoskeleton rearrangements or changes in extracellular environments. A change in spine structure may also cause an increase in spine neck conductance. Although it is unknown to what extent the increase in [Ca2+]i affects cellular chemistry, Ca2+ probably also directly/indirectly stimulates cascades which exert effects more slowly. A delayed increase in metabotropic receptor sensitivity may occur. New synthesis of protein molecules may be involved in late periods of LTP by replacing turnovered molecules and/or by supplying new materials. Some of these chains of biochemical events may also apply to presynaptic terminals, although the existence of retrograde messenger substances must still be confirmed. In addition, interactions between different protein kinases and second messengers appear to occur to bring about final effects.

Animals↗
PubMed2001

SNARE complex oligomerization by synaphin/complexin is essential for synaptic vesicle exocytosis.

Synaphin/complexin is a cytosolic protein that preferentially binds to syntaxin within the SNARE complex. We find that synaphin promotes SNAREs to form precomplexes that oligomerize into higher order structures. A peptide from the central, syntaxin binding domain of synaphin competitively inhibits these two proteins from interacting and prevents SNARE complexes from oligomerizing. Injection of this peptide into squid giant presynaptic terminals inhibited neurotransmitter release at a late prefusion step of synaptic vesicle exocytosis. We propose that oligomerization of SNARE complexes into a higher order structure creates a SNARE scaffold for efficient, regulated fusion of synaptic vesicles.

Action Potentials↗
PubMed2001

Remodeling of synaptic actin induced by photoconductive stimulation.

Use-dependent synapse remodeling is thought to provide a cellular mechanism for encoding durable memories, yet whether activity triggers an actual structural change has remained controversial. We use photoconductive stimulation to demonstrate activity-dependent morphological synaptic plasticity by video imaging of GFP-actin at individual synapses. A single tetanus transiently moves presynaptic actin toward and postsynaptic actin away from the synaptic junction. Repetitive spaced tetani induce glutamate receptor-dependent stable restructuring of synapses. Presynaptic actin redistributes and forms new puncta that label for an active synapse marker FM5-95 within 2 hr. Postsynaptic actin sprouts projections toward the new presynaptic actin puncta, resembling the axon-dendrite interaction during synaptogenesis. Our results indicate that activity-dependent presynaptic structural plasticity facilitates the formation of new active presynaptic terminals.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMedDate not supplied

The role of calcium in activity-dependent neuronal gene regulation.

Synaptic transmission is a key signaling event, whereby an action potential-induced release of chemical neurotransmitters again generates a positive or negative electrical activity via opening of postsynaptic channels. Thereafter, information spreads through space, from the postsynaptic membranes to the dendrites, to the soma, to the nucleus, to the presynaptic terminals and, in some cases, back to the originally stimulated synapses. Furthermore, information is also often converted in time, either by shifting the phase of electrical activity during the integration of EPSPs and IPSPs into the generation of an action potential, or by triggering a long-lasting cascade of enzymatic or protein-protein interaction-mediated events in the cytoplasm and in the nucleus. Recent studies of the signaling from the synapse to the nucleus now allow us to consider how various patterns of synaptic activity could couple with activation of specific nuclear transcription factors and thus regulate neuronal gene expression. The critical importance of Ca(2+)-dependent signaling processes in such regulatory events will be discussed below.

Animals↗
PubMed2002

The use of elevated divalent cation solutions to isolate monosynaptic components of sensorimotor connections in Aplysia.

A commonly used method to remove polysynaptic components of test PSPs is to elevate action potential threshold of interneurons with high extracellular concentrations of divalent cations ('Hi-Di'). Extrapolation to normal conditions requires that Hi-Di have negligible effects on synaptic transmission. We examined effects of Hi-Di on EPSPs from sensory neurons (SNs) onto motor neurons (MNs) of Aplysia in the pleural-pedal and abdominal ganglia, and in dissociated cell culture. In ganglia, standard Hi-Di solutions eliminated spontaneous input from interneurons as well as polysynaptic components of PSPs evoked by single action potentials in single SNs, but failed to block polysynaptic PSPs evoked by nerve stimulation. Hi-Di solutions had no effect on activity-dependent synaptic depression or posttetanic potentiation, or facilitation by serotonin (5-HT). Unexpectedly, standard Hi-Di solutions substantially reduced sensorimotor EPSPs in all preparations, whereas a solution containing 2.2x[Ca(2+)] and 2x[Mg(2+)] blocked the polysynaptic component of EPSPs without obvious changes to the monosynaptic component. In contrast to previous observations in Aplysia, and to predictions of the (J. Physiol. 193 (1967) 419) model, tripling the normal extracellular concentrations of Ca(2+) and Mg(2+) failed to increase sensorimotor EPSPs. Depression of EPSPs by these Hi-Di solutions may result from reduced spike invasion into presynaptic terminals.

Animals↗
PubMed1996

Calcium-independent synaptic transmission: artifact or fact?

The release of neurotransmitters at classical chemical synapses occurs via Ca2+ influx through voltage-dependent Ca2+ channels, which are opened following depolarization of presynaptic terminals. However, owing to a persistence or increase in the amount of transmitter released in preparations containing low concentrations of Ca2+, it has been proposed that transmitter release could also occur through a Ca(2+)-independent, carrier-mediated process. On the other hand, lowering extracellular [Ca2+] can actually promote Ca2+ influx through voltage-activated Ca2+ channels via a modification of the surface potential of plasma membranes. Therefore, the proposed Ca(2+)-independent transmitter release could be re-accommodated within the framework of the Ca2+ hypothesis of synaptic transmission by taking into account the surface-charge effects.

Artifacts↗
PubMed1998

Extrasynaptic glutamate spillover in the hippocampus: evidence and implications.

In the mammalian brain most excitatory transmission is mediated by glutamate binding to AMPA and NMDA receptors. These receptors have markedly different biophysical properties, and at synapses in the CAI region of the hippocampus they play complementary roles in long-term potentiation (LTP): while postsynaptic NMDA receptor activation is necessary for the induction of this form of plasticity, AMPA receptors play a larger role in its expression. Recent studies in hippocampal slices have revealed a further striking difference in the behaviour of the two receptor types: NMDA receptors consistently sense a larger number of quanta of glutamate released from presynaptic terminals than do AMPA receptors. Two alternative explanations for this are either that AMPA receptors are functionally silent at a proportion of synapses (although they can be uncovered by LTP), or that glutamate can spill over from neighbouring synapses and selectively activate NMDA (but not AMPA) receptors. Both of these competing hypotheses have extensive implications for the mechanisms of expression of LTP. Extrasynaptic glutamate diffusion appears to depend critically on the recording temperature, but if excitatory synapses are sufficiently close for cross-talk to occur under physiological conditions, it could have profound implications for the specificity of synaptic communication in the brain.

Animals↗
PubMed1998

The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease.

Synuclein proteins are produced, in vertebrates, by three genes. They share structural resemblance to apolipoproteins, but are abundant in the neuronal cytosol and present in enriched amounts at presynaptic terminals. Synucleins have been specifically implicated in three diseases:Alzheimer's (AD), Parkinson's (PD) and breast cancer. In AD, a peptide derived from alpha-synuclein forms an intrinsic component of plaque amyloid. In PD, an alpha-synuclein allele is genetically linked to several independent familial cases, and the protein appears to accumulate in Lewy bodies. In breast cancer, increased expression of gamma-synuclein correlates with disease progression. In songbirds, alpha-synuclein expression is correlated with plasticity in the developing song control system. Although the normal function of synucleins is unknown, a role in membrane plasticity seems likely.

Animals↗
PubMed2001

GABA(B(1)) mRNA expression in hippocampal sclerosis associated with human temporal lobe epilepsy.

GABA(B) receptors act to inhibit neurotransmitter release from presynaptic terminals, and mediate the late inhibitory postsynaptic potential. Studies of GABA(B) receptor function in rodent models of temporal lobe epilepsy (TLE) suggest that GABA(B) receptor expression and/or function may be perturbed. GABA(B(1)) mRNA levels were investigated in 10 hippocampal resection samples obtained at surgery from intractable hippocampal sclerosis (HS) associated TLE patients and five neurologically normal post-mortem (PM) control samples. In situ hybridisation with a 35S-dATP-labelled oligonucleotide was carried out to measure mRNA levels, along with three-dimensional cell counting, for assessment of neuronal density in hippocampal subregions. GABA(B(1)) mRNA was significantly up-regulated in the subiculum of HS samples as compared with PM controls. When adjusted for the characteristic neuronal density changes observed in HS, GABA(B(1)) mRNA was significantly up-regulated in CA1, hilus and dentate gyrus granule cell layer of HS samples as compared with PM controls. The possibility of increased GABA(B(1)) expression suggests that changes in GABA(B) receptor mechanisms may be involved in the pathogenesis of human HS-associated TLE.

Adult↗
PubMed1999

Arachidonic acid induces a long-lasting facilitation of hippocampal synaptic transmission by modulating PKC activity and nicotinic ACh receptors.

The present study was conducted to understand the effect of arachidonic acid on nicotinic acetylcholine (ACh) receptor-mediated synaptic plasticity. Arachidonic acid persistently (>/=1 h) potentiated currents through neuronal nicotinic ACh receptors (alpha7 and alpha4beta2) expressed in Xenopus oocytes, and the effect was blocked by the selective protein kinase C (PKC) inhibitors, such as GF109203X, PKCI, and co-expressed active PKC inhibitor peptide. This free fatty acid markedly increased nicotine-sensitive glutamate release from hippocampal slices and enhanced the rate of nicotine-sensitive miniature excitatory postsynaptic currents without affecting the amplitude in cultured hippocampal CA1 neurons under the influence of PKC. Furthermore, arachidonic acid induced a long-lasting (>/=3 h) facilitation of hippocampal CA1 synaptic transmission in slices, and the effect was blocked by nicotinic ACh receptor antagonists, alpha-bungarotoxin and mecamylamine. The facilitation, whereas independent of N-methyl-D-aspartate (NMDA) receptors, shares a common mechanism with long-term potentiation (LTP) induced by tetanic stimulation. The results of the present study thus suggest that arachidonic acid sustains enhanced activity of nicotinic ACh receptors by interacting with a PKC pathway, thereby increasing glutamate release from presynaptic terminals, and then leading to an 'LTP-like' facilitation of hippocampal synaptic transmission.

Animals↗
PubMedDate not supplied

Effect of fenfluramine on caloric intake and macronutrient selection in Lou/c rats during aging.

Previous studies have shown a shift of preferences from carbohydrate to fat and a decrease in protein intake in self-selected Lou/c rats with advancing age. This study investigated a potential neurochemical mechanism underlying age-related modifications by evaluating the effects of fenfluramine (dl-F), a drug that enhances 5-HT release and blocks its re-uptake by presynaptic terminals, on macronutrient selection. The drug dl-F (1.5 and 3mg/kg s.c.) induces a dose-related hypophagia with the oldest animals being the most sensitive. The main decrease is in fat consumption with minor changes in carbohydrate and protein consumptions. Young, but not old animals, compensate during the day the nocturnal intake decrease induced by dl-F. The plasma concentration of dexfenfluramine (d-F) was higher as the rats aged. The icv administrations of dl-F induced a caloric intake decrease in the oldest groups and a differential effect on protein intake between old and young rats. Metergoline induced a partial reversion of dl-F effect on food intake but this effect was not age related. These data suggest a possible implication of serotoninergic system in modifications of food behavior during aging. However, further studies are needed.

Aging↗
PubMed2002

Effect of asphyxia on the pupils of brain dead subjects.

The pupils dilate following cardiac arrest but the mechanism is unknown. If pupillary dilation represents inadequate blood supply to the midbrain, pupil size might be a rough guide to the adequacy of the resuscitation effort. The brain dead organ harvest patient presents a unique opportunity to study pupillary activity in the absence of an intact midbrain and to examine the effects of asphyxia on the pupil. Because the midbrain is dead in these subjects, the pupil has no supraspinal autonomic control and following aortic cross clamp, no blood can be delivered to the orbit. Ten brain dead patients scheduled for organ harvest were studied. Pupil size was measured from the right eye every minute for 9 min before and every minute for 10 min following aortic cross-clamp. Dapiprazole eye drops were instilled into the left eye at least 1 h before cross clamp in five cases and pupillary measurements were intermittently taken before and after cross clamp. Pupil size was stable before cross clamp. Following cross clamp, the pupil dilated in all cases, reaching 10.6 mm in one case. Mean dilation was 1.8+/-0.9 mm. Time to peak dilation was 4.3+/-1.4 min and latency of dilation was 1.4+/-1.2 min. Dapiprazole eye drops prevented the pupillary dilation in contralateral eye of the five cases in which it was used. The cause of this sympathetic activity is either a short burst of neuronal activity in the peripheral sympathetic system innervating the dilator muscle, or release of stored norepinephine from the presynaptic terminals, as asphyxia intervenes.

Adrenergic alpha-Antagonists↗
PubMed1996

The role of glutamate in the photic regulation of the suprachiasmatic nucleus.

Endogenous circadian rhythms govern most aspects of physiology and behaviour in mammals, including body temperature, autonomic and endocrine function, and sleep-wake cycles. Such rhythms are generated by the suprachiasmatic nucleus of the hypothalamus (SCN), but are synchronised to the environmental light-dark cycle by photic cues perceived by the retina and conveyed to the SCN via the retinohypothalamic tract (RHT). This review considers many lines of evidence from diverse experimental approaches indicating that the RHT employs glutamate (or a related excitatory amino acid) as a neurotransmitter. Ultrastructural studies demonstrate the presence of glutamate in presynaptic terminals within the SCN. In situ hybridisation and immunocytochemical studies reveal the presence of several NMDA (NMDAR1, NMDAR2C), non-NMDA (GluR1, GluR2, GluR4) and metabotropic (mGluR1) glutamate receptor subunits in the SCN. Messenger RNA encoding a glutamate transporter protein is also present. In behavioural tests, glutamate antagonists can block the effects of light in phase-shifting circadian rhythms. Such treatments also block the induction of c-fos within SCN cells by light, whereas a glutamate agonist (NMDA) induces c-fos expression. In hypothalamic slice preparations in vitro, electrical stimulation of the optic nerves induces release of glutamate and aspartate, and glutamate antagonists block field potentials in the SCN evoked by stimulation of the optic nerve. Circadian rhythms of electrical activity which persist in vitro are phase shifted by application of glutamate in a manner which mimics the phase shifting effects of light in vivo. This wide range of experimental findings provides strong support for the hypothesis that glutamate is the principal neurotransmitter within the RHT, and thus conveys photic cues to the circadian timing system in the SCN.

Acetylcholine↗
PubMed1998

Subspecies of protein kinase C in the rat spinal cord.

In this review, the developmental expression of alpha-, beta- and gamma-subspecies of protein kinase C (PKC) in the rat spinal cord was summarized, and possible roles of this protein for neuronal differentiation were discussed. Faint immunoreactivity (IR) for PKCs was first demonstrated in the cervical spinal cord on embryonic day 13 (E-13). It gradually became stronger, and between E-18 and postnatal day 0 (P-0), strong IR for these three subspecies was uniformly distributed throughout the spinal cord. While thereafter, it irregularly declined, and reached the adult pattern around P-28 or P-35. The motor neurons began to express these three subspecies of PKC in the nucleus, perikaryal cytoplasm, dendrites and axons, soon after they began to differentiate. In the perikaryal cytoplasm, the IR was expressed mainly on ribosomes, and in the dendrites, mainly on cytoskeletal elements. At the late embryonic and early postnatal stages, IR for these PKCs was expressed both in the presynaptic terminals and on the postsynaptic densities. While thereafter, the IR in the former declined, and was detected only on the postsynaptic densities. The dorsal corticospinal tract transiently expressed strong IR for these PKCs at the early postnatal developmental stages, but thereafter, the IR rapidly declined. The developing corticospinal tract fibers expressed strong IR mainly on cytoskeletal elements. In contrast, in the mature fibers, IR for alpha-PKC was detected on some cytoskeletal elements, and for beta-PKC on almost all cytoskeletal elements, but IR for gamma-PKC, mainly on smooth surfaced endoplasmic reticulum. These findings suggest that PKC might be involved in several aspects of neuronal differentiation such as gene expression, protein synthesis, morphological maturation and synapse formation.

Animals↗
PubMedDate not supplied

Single-file diffusion and neurotransmitter transporters: Hodgkin and Keynes model revisited.

Norepinephrine transporters (NETs) use the Na gradient to remove norepinephrine (NE) from the synaptic cleft of adrenergic neurons following NE release from the presynaptic terminal. By coupling NE to the inwardly directed Na gradient, it is possible to concentrate NE inside cells. This mechanism, which is referred to as co-transport or secondary transport (Läuger, 1991, Electrogenic Ion Pumps, Sinauer Associates) is apparently universal: Na coupled transport applies to serotonin transporters (SERTs), dopamine transporters (DATs), glutamate transporters, and many others, including transporters for osmolites, metabolites and substrates such as sugar. Recently we have shown that NETs and SERTs transport norepinephrine or serotonin as if Na and the transmitter permeated through an ion channel together 'Galli et al., 1998, PNAS 95, 13260-13265; Petersen and DeFelice, 1999, Nature Neurosci. 2, 605-610'. These data are paradoxical because it has been difficult to envisage how NE, for example, would couple to Na if these ions move passively through an open pore. An 'alternating access' model is usually evoked to explain coupling: in such models NE and Na bind to NET, which then undergoes a conformational change to release NE and Na on the inside. The empty transporter then turns outward to complete the cycle. Alternating-access models never afford access to an open channel. Rather, substrates and co-transported ions are occluded in the transporter and carried across the membrane. The coupling mechanism we propose is fundamentally different than the coupling mechanism evoked in the alternating access model. To explain coupling in co-transporters, we use a mechanism first evoked by 'Hodgkin and Keynes (1955) J. Physiol. 128, 61-88' to explain ion interactions in K-selective channels. In the Hodgkin and Keynes model, K ions move single-file through a long narrow pore. Their model accounted for the inward/outward flux ratio if they assumed that two K ions queue within the pore. We evoke a similar model for the co-transport of transmitter and Na. In our case, however, coupling occurs not only between like ions but also between unlike ions (i.e. the transmitter and Na ). We made a replica of the Hodgkin and Keynes mechanical model to test our ideas, and we extended the model with computer simulations using Monte Carlo methods. We also developed an analytic formula for Na coupled co-transport that is analogous to the single-file Ussing equation for channels. The model shows that stochastic diffusion through a long narrow pore can explain coupled transport. The length of the pore amplifies the Na gradient that drives co-transport.

Computer Simulation↗