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Results for “Presynaptic Terminals”

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At least 865 records · Page 48Linked to original sources
PubMed1994

Pharmacological identification of two types of presynaptic voltage-dependent calcium channels at CA3-CA1 synapses of the hippocampus.

The effects of voltage-dependent Ca channel (VDCC) antagonists on synaptic transmission were investigated at CA3-CA1 synapses of guinea pig hippocampal slices. After selectively loading presynaptic structures in area CA1 with the calcium indicator fura-2, we simultaneously recorded a presynaptic calcium transient ([Ca]t) and the corresponding field excitatory postsynaptic potential (fEPSP) evoked by a single stimulus given to the Schaffer collateral-commissural (SCC) pathway. Application of nifedipine did not reduce either the [Ca]t of the fEPSP, suggesting that nifedipine-sensitive Ca channels do not significantly contribute to evoked synaptic transmission at low stimulation frequency. Application of omega-conotoxin GVIA (omega-CgTX) or omega-agatoxin-IVA (omega-Aga-IVA) dose-dependently blocked both the [Ca]t and the fEPSP. The time course of the block of the [Ca]t was similar to that of the fEPSP. About 40% of the total [Ca]t was omega-CgTX sensitive, and more than 20% was omega-Aga-IVA sensitive. Combined application of these two blockers showed no overlap of the omega-CgTX-sensitive with the omega-Aga-IVA-sensitive [Ca]t. These results suggest that there are at least two types of presynaptic VDCCs at CA3-CA1 synapses of the hippocampus: omega-CgTX-sensitive and omega-Aga-IVA-sensitive Ca channels. Our results also suggest that these two types of Ca channels are colocalized at a single presynaptic terminal. During application of omega-CgTX or omega-Aga-IVA, the initial slope of the fEPSP varied approximately as the fourth power of the amplitude of the [Ca]t, suggesting that omega-CgTX-sensitive and omega-Aga-IVA-sensitive Ca channels have about equal efficacy in triggering transmitter release. These results in combination with similar findings at the squid giant synapse suggest that the nonlinear relationship between transmitter release and the Ca influx is well conserved from the molluscan to the mammalian nervous system.

Animals↗
PubMed1999

Postnatal development of synaptophysin immunoreactivity in the rat nucleus tractus solitarii and caudal ventrolateral medulla.

Synaptophysin (SY) is a major integral membrane protein of small synaptic vesicles. In the present study, SY immunohistochemistry was used to investigate the postnatal development of the rat nucleus tractus solitarii (NTS) and nucleus ambiguus/ventrolateral medulla (NA/VLM). Whatever the age of the animal, SY immunoreactivity showed a typical pattern of punctate staining reminiscent of presynaptic terminal labeling. In the NTS and the NA/VLM, SY immunoreactive puncta were few at birth and increased in number during the first postnatal days. These changes were quantified by measuring the volumetric fraction occupied by SY immunoreactive puncta at various postnatal ages. Using volumetric fraction data, an index of the total volume occupied SY immunoreactivity in each region was then calculated. Between birth and adulthood, this index increased by 6-fold in the NTS and by 7-fold in the NA/VLM, suggesting that most of the synaptic development of these regions occurs postnatally.

Aging↗
PubMed2006

Software for simulating calcium-triggered exocytotic processes.

We describe a software package for the simulation of exocytotic events from readily releasable pools of secretory vesicles in neuroendocrine cells and presynaptic terminals. The visual package Ca3D_Exolab simulates the entry of Ca(2+) through the calcium channels, the kinetic reactions of calcium with buffers, the diffusion of calcium and mobile buffers, and the kinetic reactions of calcium with the secretory vesicles. The location of both channels and secretory vesicles can be set by using a graphical interface. Calcium and buffer concentrations at different depths from the cellular membrane and capacitance time courses are obtained as outputs. The software package also provides a descriptive statistical data analysis of the different output data.

Calcium↗
PubMed1999

Prolonged activation of mitochondrial conductances during synaptic transmission.

Although ion channels have been detected in mitochondria, scientists have not been able to record ion transport in mitochondria of intact cells. A variation of the patch clamp technique was used to record ion channel activity from intracellular organelles in the presynaptic terminal of the squid. Electron microscopy indicated that mitochondria are numerous in this terminal and are the only organelles compatible with the tips of the pipettes. Before synaptic stimulation, channel activity was infrequent and its conductance was small, although large conductances ( approximately 0.5 to 2.5 nanosiemens) could be detected occasionally. During a train of action potentials, the conductance of the mitochondrial membrane increased up to 60-fold. The conductance increased after a delay of several hundred milliseconds and continued to increase after stimulation had stopped. Recovery occurred over tens of seconds.

Action Potentials↗
PubMed2006

The synaptic vesicle: cycle of exocytosis and endocytosis.

Synaptic vesicles are clustered at the presynaptic terminal where they fuse and recycle in response to stimulation. Vesicles appear to be sorted into pools, but we do not yet understand how physiologically defined pools relate to morphological pools. The advent of dynamic imaging approaches has led to an appreciation of the regulation of vesicle mobility. Newly endocytosed vesicles are highly mobile but appear to become transiently trapped as they re-enter the recycling pool. Recent experiments indicate that endocytosis might have a constant rate, but limited capacity. How endocytosis is linked to exocytosis remains unclear, although calcium emerges as an important player.

Action Potentials↗
PubMed2002

Glutamate receptor trafficking in synaptic plasticity.

Ionotropic glutamate receptors mediate excitatory synaptic transmission at most central mammalian synapses. In addition to converting the chemical signal released from the presynaptic terminal to an electrical response in the postsynaptic neuron, these receptors are critically involved in activity-dependent, long-term changes in synaptic strength and, therefore, are central to processes thought to underlie learning and memory. Several mechanisms have been proposed to play roles in altering synaptic strength, and it is clear that there are several different forms of long-term synaptic plasticity in the mammalian brain. Here, we review recent evidence that some forms of synaptic strengthening rely on the modification of the glutamate receptor complement at synapses in response to activity-dependent processes.

Animals↗
PubMed2003

Mobility and cycling of synaptic protein-containing vesicles in axonal growth cone filopodia.

The spatial distribution and coordination of vesicular dynamics within growth cones are poorly understood. It has long been thought that membranous organelles are concentrated in the central regions of growth cones and excluded from filopodia; this view has dramatically shaped conceptual models of the cellular mechanisms of axonal growth and presynaptic terminal formation. To begin to test these models, we studied membrane dynamics within axonal growth cones of living rat cortical neurons. We demonstrate that growth cone filopodia contain vesicles that transport synaptic vesicle proteins bidirectionally along filopodia and fuse with the filopodial surface in response to focal stimulation, allowing for both local secretion of vesicular contents and rapid changes in the plasma membrane composition of individual filopodia. Our results suggest a new model in which growth cone filopodia are actively involved in both emitting and responding to local signals related to axon growth and early synapse formation.

Animals↗
PubMed2003

Involvement of actin polymerization in vesicle recruitment at the calyx of Held synapse.

Depletion and replenishment of pools of synaptic vesicles are important determinants of short-term synaptic plasticity, but the underlying molecular mechanisms are not yet clear. As a first step toward understanding the process of vesicle recruitment, we have applied various specific agents directly to the presynaptic terminal of the calyx of Held synapse. Here we show that the nonhydrolyzable ATP analog ATP-gammaS retards the recovery from vesicle pool depletion, as does latrunculin A. Phalloidin has no effects on recovery, suggesting that dynamic actin reorganization is not necessary. Unexpectedly, neither N-ethylmaleimide nor staurosporine affected the recovery, calling into question the role of N-ethylmaleimide-sensitive factor and protein kinases. The results suggest that intact actin polymerization is involved in vesicle recruitment.

Actins↗
PubMed2005

Presynaptic Ca2+ dynamics, Ca2+ buffers and synaptic efficacy.

In synapses neurotransmitter release is triggered by elevation of Ca2+ concentration at a Ca2+ sensor of the release machinery. The Ca2+ concentration at the release site at the given time point is determined by Ca2+ dynamics within presynaptic terminal. It depends on a source of Ca2+ (usually voltage-gated Ca2+ channels), diffusional distance between the source of Ca2+ and the Ca2+ sensor and Ca2+ buffering by endogenous Ca2+ buffers. In many synapses transmitter release can be enhanced (facilitated) during repetitive activity of neurons. The main source of facilitation is activity-dependent increase of Ca2+ concentration at the release site. Several mechanisms of facilitation have been proposed, namely, accumulation of residual Ca2+, multi-site (X receptor) mechanism and partial Ca2+ buffer saturation mechanism. In this review we discuss theoretical and experimental evidence in favor of one or the other of proposed mechanisms.

Animals↗
PubMed1997

Role of Drosophila alpha-adaptin in presynaptic vesicle recycling.

Rapid flow of information in the nervous system involves presynaptic vesicle recycling by clathrin-mediated endocytosis, an event triggered by the alpha-adaptin-containing AP2 complex. We identified a Drosophila alpha-adaptin expressed in the garland cells, imaginal discs, and the CNS. Here we show its role in presynaptic vesicle recycling. In presynaptic terminals, alpha-adaptin defines a network-like membrane structure to which the GTPase dynamin is recruited. alpha-adaptin is necessary for the formation of clathrin-coated pits and participates in the dynamin-dependent release of coated vesicles from the membrane surface. Our results suggest an alpha-adaptin-dependent control of the vesicle cycle that maintains the balance between the amount of vesicle- and surface-associated membranes.

Adaptor Protein Complex 2↗
PubMed1996

Determinants of the time course of facilitation at the granule cell to Purkinje cell synapse.

Short-term facilitation is a widely observed form of synaptic enhancement that is not well understood. Although presynaptic calcium has long been implicated in this process, its role is unclear, particularly at synapses in the mammalian brain. We tested the role of presynaptic residual free calcium ([Ca]res) in facilitation of synapses between granule cells and Purkinje cells in rat cerebellar slices. Paired-pulse facilitation of synaptic currents resulted in an approximately 2.5-fold enhancement that decayed with a time constant of approximately 200 msec, as assessed by voltage-clamp recordings. Measurements of [Ca]res using fluorescent calcium-sensitive indicators revealed that [Ca]res decayed more rapidly than did facilitation. Manipulation of [Ca]res dynamics by introducing EGTA into presynaptic terminals sped the decays of [Ca]res and facilitation in a dose-dependent manner. When [Ca]res was reduced to a brief impulse lasting several milliseconds, facilitation was still present, although reduced in amplitude and duration. Facilitation decayed with an intrinsic time constant of approximately 40 msec. These results suggest that facilitation at this synapse is produced by a calcium-driven process with a high affinity and a slow effective off-rate. A combination of [Ca]res dynamics and the properties of a calcium-driven reaction determine the time course and amplitude of facilitation.

Animals↗
PubMed1994

The nucleus basalis of Meynert of the human brain: a Golgi and electron microscope study.

The nucleus basalis of Meynert of normal brains, aged from 15 to 73 years was studied in Golgi preparations and in electron microscopy. The nucleus is composed of large triangular, polyhedral and bipolar cells which are intermixed with numerous small or medium-sized spiny neurons. All of the neurons form a dense three dimensional dendritic arborization, with numerous secondary and tertiary dendritic branches studded with spines. The ultrastructural analysis revealed numerous axodendritic and axosomatic synapses between the spines. The ultrastructural analysis revealed numerous axodendritic and axosomatic synapses between the spiny neurons and the large triangular and polyhedral neurons. The presynaptic axonic profiles are plenty of ellipsoid and round synaptic vesicles. Large presynaptic terminals are seen frequently surrounded by numerous dendritic spines forming synaptic glomeruli, in all the areas of the nucleus basalis of Meynert. An age depended decrease of the number of neurons was noticed affecting mainly the population of the spiny neurons. Although in senile and presenile dementias an impressive loss of the cholinergic neurons of the nucleus basalis was reported, in normal aging the large cholinergic neurons of the nucleus basalis seems to be intact, whereas the medium and small shaped spiny neurons are decreased in number suggesting that the GABA-ergic neurons are principally affected.

Adolescent↗
PubMed2000

Zn(2+): a novel ionic mediator of neural injury in brain disease.

Zn(2+) is the second most prevalent trace element in the body and is present in particularly large concentrations in the mammalian brain. Although Zn(2+) is a cofactor for many enzymes in all tissues, a unique feature of brain Zn(2+) is its vesicular localization in presynaptic terminals, where its release is dependent on neural activity. Although the physiological significance of synaptic Zn(2+) release is little understood, it probably plays a modulatory role in synaptic transmission. Furthermore, several lines of evidence support the idea that, upon excessive synaptic Zn(2+) release, its accumulation in postsynaptic neurons contributes to the selective neuronal loss that is associated with certain acute conditions, including epilepsy and transient global ischaemia. More speculatively, Zn(2+) dis-homeostasis might also contribute to some degenerative conditions, including Alzheimer's disease. Further elucidation of the pathological actions of Zn(2+) in the brain should result in new therapeutic approaches to these conditions.

Animals↗
PubMed2003

Pentobarbitone modulates calcium transients in axons and synaptic boutons of hippocampal CA1 neurons.

Although barbiturates, like other general anaesthetics, depress excitatory synaptic transmission in the central nervous system (CNS), the underlying cellular mechanisms remain unresolved. They may increase the likelihood that an action potential will fail to invade every branch of the axonal arbour, thereby decreasing the synaptic drive to the postsynaptic neurons. Alternatively, they may inhibit calcium entry into the presynaptic terminals, thus reducing transmitter release. To resolve these issues, we have used two-photon microscopy to monitor calcium transients evoked by action potentials in axons, axonal varicosities (synaptic boutons) and fine axon collaterals of hippocampal CA1 neurons. Pentobarbitone (75-300 microM) did not block the invasion of the axonal arbour or the synaptic boutons, but it did reduce the amplitude of the calcium transients recorded from the axons in a concentration-dependent manner. At 150 microM, pentobarbitone reduced the transients to 78+/-4% of the control. Pentobarbitone depressed the calcium transients recorded from the synaptic boutons in a concentration-dependent manner. When 150 microM pentobarbitone was applied, the calcium transients recorded from the boutons were 53+/-3% of the control. This concentration of pentobarbitone also reduced the amplitude and frequency of the spontaneous excitatory postsynaptic potentials to 54+/-4 and 42+/-17% of the control, respectively. The local anaesthetic procaine (500 microM) had no significant effect on action potential invasion of axon collaterals, even though it reduced the action potential amplitude by 25%. This data are consistent with the notion that the pentobarbitone-induced depression of presynaptic calcium transients contributes to its depressant effect on excitatory synaptic transmission in the CNS.

Action Potentials↗
PubMed1997

Vesicular acetylcholine transport inhibitor suppresses REM sleep.

The vesamicol-like compound (+/-)-4-aminobenzovesamicol (ABV) non-competitively inhibits vesicular packaging of acetylcholine (ACh) in presynaptic terminals. This study tested the hypothesis that microinjection of ABV into the medial pontine reticular formation (mPRF) of intact, unanesthetized cats would inhibit rapid eye movement (REM) sleep. Microinjection of ABV alone or before administration of the acetylcholinesterase inhibitor neostigmine was used to evaluate the effects of ABV on natural REM sleep and on the neostigmine-induced REM sleep-like state. ABV decreased (24.8%) REM sleep and significantly reduced (33.6%) the neostigmine-induced REM sleep-like state. The results show for the first time that REM sleep generation can be disrupted by blocking a synaptic vesicle protein that modulates ACh transport in localized regions of the mPRF.

Acetylcholine↗
PubMed2006

Complete dissociation of motor neuron death from motor dysfunction by Bax deletion in a mouse model of ALS.

The death of cranial and spinal motoneurons (MNs) is believed to be an essential component of the pathogenesis of amyotrophic lateral sclerosis (ALS). We tested this hypothesis by crossing Bax-deficient mice with mice expressing mutant superoxide dismutase 1 (SOD1), a transgenic model of familial ALS. Although Bax deletion failed to prevent neuromuscular denervation and mitochondrial vacuolization, MNs were completely rescued from mutant SOD1-mediated death. However, Bax deficiency extended lifespan and delayed the onset of motor dysfunction of SOD1 mutants, suggesting that Bax acts via a mechanism distinct from cell death activation. Consistent with this idea, Bax elimination delayed the onset of neuromuscular denervation, which began long before the activation of cell death proteins in SOD1 mutants. Additionally, we show that denervation preceded accumulation of mutant SOD1 within MNs and astrogliosis in the spinal cord, which are also both delayed in Bax-deficient SOD1 mutants. Interestingly, MNs exhibited mitochondrial abnormalities at the innervated neuromuscular junction at the onset of neuromuscular denervation. Additionally, both MN presynaptic terminals and terminal Schwann cells expressed high levels of mutant SOD1 before MNs withdrew their axons. Together, these data support the idea that clinical symptoms in the SOD1 G93A model of ALS result specifically from damage to the distal motor axon and not from activation of the death pathway, and cast doubt on the utility of anti-apoptotic therapies to combat ALS. Furthermore, they suggest a novel, cell death-independent role for Bax in facilitating mutant SOD1-mediated motor denervation.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Ischemia-induced modifications in hippocampal CA1 stratum radiatum excitatory synapses.

Relatively mild ischemic episode can initiate a chain of events resulting in delayed cell death and significant lesions in the affected brain regions. We studied early synaptic modifications after brief ischemia modeled in rats by transient vessels' occlusion in vivo or oxygen-glucose deprivation in vitro and resulting in delayed death of hippocampal CA1 pyramidal cells. Electron microscopic analysis of excitatory spine synapses in CA1 stratum radiatum revealed a rapid increase of the postsynaptic density (PSD) thickness and length, as well as formation of concave synapses with perforated PSD during the first 24 h after ischemic episode, followed at the long term by degeneration of 80% of synaptic contacts. In presynaptic terminals, ischemia induced a depletion of synaptic vesicles and changes in their spatial arrangement: they became more distant from active zones and had larger intervesicle spacing compared to controls. These rapid structural synaptic changes could be implicated in the mechanisms of cell death or adaptive plasticity. Comparison of the in vivo and in vitro model systems used in the study demonstrated a general similarity of these early morphological changes, confirming the validity of the in vitro model for studying synaptic structural plasticity.

Animals↗
PubMed1998

Regulation of neurotransmitter release kinetics by NSF.

NSF (N-ethylmaleimide-sensitive factor) is an adenosine triphosphatase (ATPase) that contributes to a protein complex essential for membrane fusion. The synaptic function of this protein was investigated by injecting, into the giant presynaptic terminal of squid, peptides that inhibit the ATPase activity of NSF stimulated by the soluble NSF attachment protein (SNAP). These peptides reduced the amount and slowed the kinetics of neurotransmitter release as a result of actions that required vesicle turnover and occurred at a step subsequent to vesicle docking. These results define NSF as an essential participant in synaptic vesicle exocytosis that regulates the kinetics of neurotransmitter release and, thereby, the integrative properties of synapses.

Adenosine Triphosphatases↗