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Shasta L Sabo - One of the best experts on this subject based on the ideXlab platform.
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Spatio-temporal dynamics of neocortical Presynaptic Terminal development using multi-photon imaging of the corpus callosum in vivo.
Scientific reports, 2019Co-Authors: Teresa A. Evans, Luke A D Bury, Alex Yee-chen Huang, Shasta L SaboAbstract:Within the developing central nervous system, the dynamics of synapse formation and elimination are insufficiently understood. It is ideal to study these processes in vivo, where neurons form synapses within appropriate behavioral and anatomical contexts. In vivo analysis is particularly important for long-range connections, since their development cannot be adequately studied in vitro. The corpus callosum (CC) represents a clinically-relevant long-range connection since several neurodevelopmental diseases involve CC defects. Here, we present a novel strategy for in vivo longitudinal and rapid time-lapse imaging of CC Presynaptic Terminal development. In postnatal mice, the time-course of CC Presynaptic Terminal formation and elimination was highly variable between axons or groups of axons. Young Presynaptic Terminals were remarkably dynamic – moving, dividing to generate more boutons, and merging to consolidate small Terminals into large boutons. As synaptic networks matured, Presynaptic mobility decreased. These rapid dynamics may be important for establishing initial synaptic contacts with postsynaptic partners, refining connectivity patterns or modifying synapse strength during development. Ultimately, this in vivo imaging approach will facilitate investigation of synapse development in other long-range connections and neurodevelopmental disease models.
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building a Terminal mechanisms of Presynaptic development in the cns
The Neuroscientist, 2016Co-Authors: Luke A D Bury, Shasta L SaboAbstract:To create a Presynaptic Terminal, molecular signaling events must be orchestrated across a number of subcellular compartments. In the soma, Presynaptic proteins need to be synthesized, packaged together, and attached to microtubule motors for shipment through the axon. Within the axon, transport of Presynaptic packages is regulated to ensure that developing synapses receive an adequate supply of components. At individual axonal sites, extracellular interactions must be translated into intracellular signals that can incorporate mobile transport vesicles into the nascent Presynaptic Terminal. Even once the initial recruitment process is complete, the components and subsequent functionality of Presynaptic Terminals need to constantly be remodeled. Perhaps most remarkably, all of these processes need to be coordinated in space and time. In this review, we discuss how these dynamic cellular processes occur in neurons of the central nervous system in order to generate Presynaptic Terminals in the brain.
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dynamic mechanisms of neuroligin dependent Presynaptic Terminal assembly in living cortical neurons
Neural Development, 2014Co-Authors: Luke A D Bury, Shasta L SaboAbstract:Background Synapse formation occurs when synaptogenic signals trigger coordinated development of pre and postsynaptic structures. One of the best-characterized synaptogenic signals is trans-synaptic adhesion. However, it remains unclear how synaptic proteins are recruited to sites of adhesion. In particular, it is unknown whether synaptogenic signals attract synaptic vesicle (SV) and active zone (AZ) proteins to nascent synapses or instead predominantly function to create sites that are capable of forming synapses. It is also unclear how labile synaptic proteins are at developing synapses after their initial recruitment. To address these issues, we used long-term, live confocal imaging of Presynaptic Terminal formation in cultured cortical neurons after contact with the synaptogenic postsynaptic adhesion proteins neuroligin-1 or SynCAM-1.
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Dynamic mechanisms of neuroligin-dependent Presynaptic Terminal assembly in living cortical neurons
Neural Development, 2014Co-Authors: Luke A D Bury, Shasta L SaboAbstract:Background Synapse formation occurs when synaptogenic signals trigger coordinated development of pre and postsynaptic structures. One of the best-characterized synaptogenic signals is trans-synaptic adhesion. However, it remains unclear how synaptic proteins are recruited to sites of adhesion. In particular, it is unknown whether synaptogenic signals attract synaptic vesicle (SV) and active zone (AZ) proteins to nascent synapses or instead predominantly function to create sites that are capable of forming synapses. It is also unclear how labile synaptic proteins are at developing synapses after their initial recruitment. To address these issues, we used long-term, live confocal imaging of Presynaptic Terminal formation in cultured cortical neurons after contact with the synaptogenic postsynaptic adhesion proteins neuroligin-1 or SynCAM-1. Results Surprisingly, we find that trans-synaptic adhesion does not attract SV or AZ proteins nor alter their transport. In addition, although neurexin (the Presynaptic partner of neuroligin) typically accumulates over the entire region of contact between axons and neuroligin-1-expressing cells, SV proteins selectively assemble at spots of enhanced neurexin clustering. The arrival and maintenance of SV proteins at these sites is highly variable over the course of minutes to hours, and this variability correlates with neurexin levels at individual synapses. Conclusions Together, our data support a model of synaptogenesis where Presynaptic proteins are trapped at specific axonal sites, where they are stabilized by trans-synaptic adhesion signaling.
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developmental up regulation of vesicular glutamate transporter 1 promotes neocortical Presynaptic Terminal development
PLOS ONE, 2012Co-Authors: Corbett T Berry, Michael P Sceniak, Louie Zhou, Shasta L SaboAbstract:Presynaptic Terminal formation is a complex process that requires assembly of proteins responsible for synaptic transmission at sites of axo-dendritic contact. Accumulation of Presynaptic proteins at developing Terminals is facilitated by glutamate receptor activation. Glutamate is loaded into synaptic vesicles for release via the vesicular glutamate transporters VGLUT1 and VGLUT2. During postnatal development there is a switch from predominantly VGLUT2 expression to high VGLUT1 and low VGLUT2, raising the question of whether the developmental increase in VGLUT1 is important for Presynaptic development. Here, we addressed this question using confocal microscopy and quantitative immunocytochemistry in primary cultures of rat neocortical neurons. First, in order to understand the extent to which the developmental switch from VGLUT2 to VGLUT1 occurs through an increase in VGLUT1 at individual Presynaptic Terminals or through addition of VGLUT1-positive Presynaptic Terminals, we examined the spatio-temporal dynamics of VGLUT1 and VGLUT2 expression. Between 5 and 12 days in culture, the percentage of Presynaptic Terminals that expressed VGLUT1 increased during synapse formation, as did expression of VGLUT1 at individual Terminals. A subset of VGLUT1-positive Terminals also expressed VGLUT2, which decreased at these Terminals. At individual Terminals, the increase in VGLUT1 correlated with greater accumulation of other synaptic vesicle proteins, such as synapsin and synaptophysin. When the developmental increase in VGLUT1 was prevented using VGLUT1-shRNA, the density of Presynaptic Terminals and accumulation of synapsin and synaptophysin at Terminals were decreased. Since VGLUT1 knock-down was limited to a small number of neurons, the observed effects were cell-autonomous and independent of changes in overall network activity. These results demonstrate that up-regulation of VGLUT1 is important for development of Presynaptic Terminals in the cortex.
Hiromu Yawo - One of the best experts on this subject based on the ideXlab platform.
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Optogenetic Probing and Manipulation of the Calyx-Type Presynaptic Terminal in the Embryonic Chick Ciliary Ganglion
PloS one, 2013Co-Authors: Ryo Egawa, Shoko Hososhima, Xubin Hou, Hidetaka Katow, Toru Ishizuka, Harukazu Nakamura, Hiromu YawoAbstract:The calyx-type synapse of chick ciliary ganglion (CG) has been intensively studied for decades as a model system for the synaptic development, morphology and physiology. Despite recent advances in optogenetics probing and/or manipulation of the elementary steps of the transmitter release such as membrane depolarization and Ca(2+) elevation, the current gene-manipulating methods are not suitable for targeting specifically the calyx-type Presynaptic Terminals. Here, we evaluated a method for manipulating the molecular and functional organization of the Presynaptic Terminals of this model synapse. We transfected progenitors of the Edinger-Westphal (EW) nucleus neurons with an EGFP expression vector by in ovo electroporation at embryonic day 2 (E2) and examined the CG at E8-14. We found that dozens of the calyx-type Presynaptic Terminals and axons were selectively labeled with EGFP fluorescence. When a Brainbow construct containing the membrane-tethered fluorescent proteins m-CFP, m-YFP and m-RFP, was introduced together with a Cre expression construct, the color coding of each Presynaptic axon facilitated discrimination among inter-tangled projections, particularly during the developmental re-organization period of synaptic connections. With the simultaneous expression of one of the chimeric variants of channelrhodopsins, channelrhodopsin-fast receiver (ChRFR), and R-GECO1, a red-shifted fluorescent Ca(2+)-sensor, the Ca(2+) elevation was optically measured under direct photostimulation of the Presynaptic Terminal. Although this optically evoked Ca(2+) elevation was mostly dependent on the action potential, a significant component remained even in the absence of extracellular Ca(2+). It is suggested that the photo-activation of ChRFR facilitated the release of Ca(2+) from intracellular Ca(2+) stores directly or indirectly. The above system, by facilitating the molecular study of the calyx-type Presynaptic Terminal, would provide an experimental platform for unveiling the molecular mechanisms underlying the morphology, physiology and development of synapses.
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involvement of cgmp dependent protein kinase in adrenergic potentiation of transmitter release from the calyx type Presynaptic Terminal
The Journal of Neuroscience, 1999Co-Authors: Hiromu YawoAbstract:I have previously reported that norepinephrine (NE) induces a sustained potentiation of transmitter release in the chick ciliary ganglion through a mechanism pharmacologically distinct from any known adrenergic receptors. Here I report that the adrenergic potentiation of transmitter release was enhanced by a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX) and by zaprinast, an inhibitor of cGMP-selective phosphodiesterase. Exogenous application of the membrane-permeable cGMP, 8-bromo-cGMP (8Br-cGMP), potentiated the quantal transmitter release, and after potentiation, the addition of NE was no longer effective. On the other hand, 8Br-cAMP neither potentiated the transmitter release nor occluded the NE-induced potentiation. The NE-induced potentiation was blocked by neither nitric oxide (NO) synthase inhibitor nor NO scavenger. The quantal transmitter release was not potentiated by NO donors, e.g., sodium nitroprusside. The NE-induced potentiation and its enhancement by IBMX was antagonized by two inhibitors of protein kinase G (PKG), Rp isomer of 8-(4-chlorophenylthio) guanosine-3′,5′-cyclic monophosphorothioate and KT5823. As with NE-induced potentiation, the effects of 8Br-cGMP on both the resting intraTerminal [Ca2+] ([Ca2+]i) and the action potential-dependent increment of [Ca2+]i (ΔCa) in the Presynaptic Terminal were negligible. The reduction of the paired pulse ratio of EPSC is consistent with the notion that the NE- and cGMP-dependent potentiation of transmitter release was attributable mainly to an increase of the exocytotic fusion probability. These results indicate that NE binds to a novel adrenergic receptor that activates guanylyl cyclase and that accumulation of cGMP activates PKG, which may phosphorylate a target protein involved in the exocytosis of synaptic vesicles.
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two components of transmitter release from the chick ciliary Presynaptic Terminal and their regulation by protein kinase c
The Journal of Physiology, 1999Co-Authors: Hiromu YawoAbstract:1. A study was made of the effects of phorbol ester (phorbol 12-myristate 13-acetate, PMA, 0.1 microM) on the two components of evoked transmitter release, namely the fast synchronous and the slow asynchronous components, from the giant Presynaptic Terminal of the chick ciliary ganglion. The excitatory postsynaptic currents (EPSCs) were recorded under whole-cell voltage clamp of the postsynaptic neuron. 2. The decay time constant of the slow component was prolonged by replacing Ca2+ with Sr2+. In 5 mM [Sr2+]o the fast component decayed with a time constant of 2.6 +/- 1.4 ms whereas the slow component decayed with a time constant of 19 +/- 7 ms. 3. When stimulated with twin pulses with a short interpulse interval, the fast component of the second EPSC was often depressed whereas the slow component was usually facilitated. Both components were positively dependent on [Sr2+]o in a saturable manner, but the fast component approached its maximum at a lower [Sr2+]o than the slow component. 4. PMA potentiated both the fast and slow components to a similar extent and with a similar time course. For each component, the effect of PMA was less potent at high [Sr2+]o than at low [Sr2+]o. For either the fast or the slow component the PMA-induced potentiation was accompanied by a reduction in the paired-pulse ratio (PPR). 5. Despite the different dissociation constant for dextran-conjugated fura-2, the fluorescent ratio for intraTerminal [Sr2+] ([Sr2+]i) decayed to the baseline after the nerve-evoked increment with a time course similar to that for [Ca2+]i, suggesting that intraTerminal Sr2+ is buffered less efficiently than Ca2+. PMA did not increase the [Sr2+]i transients produced by stimulation of the Presynaptic oculomotor nerve. 6. It is suggested that protein kinase C (PKC) modulates both the fast and slow components through common molecular mechanisms that upregulate the Sr2+ sensitivity of the vesicle fusion probability.
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protein kinase c potentiates transmitter release from the chick ciliary Presynaptic Terminal by increasing the exocytotic fusion probability
The Journal of Physiology, 1999Co-Authors: Hiromu YawoAbstract:The giant Presynaptic Terminal of chick ciliary ganglion was used to examine how protein kinase C (PKC) modulates neurotransmitter release. Cholinergic excitatory postsynaptic currents (EPSCs) were recorded under whole-cell voltage clamp. Although the EPSC was potentiated by phorbol ester (phorbol 12-myristate 13-acetate, PMA; 0.1 μm) in a sustained manner, the nicotine-induced current was unaffected. PMA increased the quantal content to 2.4 ± 0.4 (n = 9) of control without changing the quantal size. The inactive isoform of PMA, 4α-PMA, showed no significant effect on EPSCs. The PMA-induced potentiation was antagonized by two PKC inhibitors with different modes of action, sphingosine (20 μm) and bisindolylmaleimide I (10 μm). When stimulated by twin pulses of short interval, the second EPSC was on average larger than the first EPSC (paired-pulse facilitation; PPF). PMA significantly decreased the PPF ratio with a time course similar to that of the potentiation of the first EPSC. PMA did not affect resting [Ca2+]i or the action potential-induced [Ca2+]i increment in the giant Presynaptic Terminals. The effect of PMA was less at 10 mm[Ca2+]o than at 1 mm[Ca2+]o. When a train of action potentials was generated with a short interval, the EPSC was eventually depressed and reached a steady-state level. The recovery process followed a simple exponential relation with a rate constant of 0.132 ± 0.029 s−1. PMA did not affect the recovery rate constant of EPSCs from tetanic depression. In addition, PMA did not affect the steady-state EPSC which should be proportional to the refilling rate of the readily releasable pool of vesicles. These results conflict with the hypothesis that PKC upregulates the size of the readily releasable pool or the number of release sites. PKC appears to upregulate the Ca2+ sensitivity of the process that controls the exocytotic fusion probability. Protein kinase C (PKC) has been implicated as having pivotal roles in the regulation of signal transduction (Nishizuka, 1992). Activation of PKC has been shown to be involved in the modulation of synaptic transmission by a variety of signals (Tanaka & Nishizuka, 1994). It has been suggested that PKC may enhance synaptic transmission via a Presynaptic mechanism. In hippocampal CA3 pyramidal neurones, the mossy fibre output is potentiated by phorbol esters in a PKC-dependent manner (Yamamoto et al. 1987; Son & Carpenter, 1996). PKC also potentiates transmitter release from cholinergic nerve Terminals of autonomic ganglia and neuromuscular junctions (Minota et al. 1991; Bachoo et al. 1992; Somogyi et al. 1996; Redman et al. 1997). The state- and/or time-dependent facilitation of transmitter release from Aplysia sensory neurones is mediated by PKC (Byrne & Kandel, 1996). How does PKC potentiate transmitter release from nerve Terminals? PKC may increase Ca2+ influx during the action potential either through activation of voltage-dependent Ca2+ channels (Doerner et al. 1990; Schroeder et al. 1990; Swartz, 1993; Zhu & Ikeda, 1994; Stea et al. 1995) or through suppression of K+ channels (Bowlby & Levitan, 1995). This is consistent with the observation that PKC-dependent potentiation is often accompanied by a reduction in paired-pulse facilitation (PPF) (Zalutsky & Nicoll, 1990). Alternatively, PKC may directly modulate the exocytosis of synaptic vesicles downstream of Ca2+ entry (Redman et al. 1997). Phorbol esters increase the frequency of spontaneous miniature inhibitory postsynaptic currents in CA3 pyramidal neurones through a Ca2+-independent mechanism (Capogna et al. 1995), whereas in CA1 pyramidal neurones they increase the frequency of miniature excitatory postsynaptic currents (EPSCs) through both Ca2+-dependent and -independent mechanisms (Parfitt & Madison, 1993). One objective of the present study was to determine whether the PKC-dependent potentiation of nerve-evoked transmitter release is accompanied by an increase in Ca2+ influx in the giant Presynaptic Terminal of chick ciliary ganglion. To this end, the intraTerminal Ca2+ concentration ([Ca2+]i) was measured directly (Yawo & Chuhma, 1993, 1994). If PKC activation increases the evoked transmitter release without altering [Ca2+]i, this would indicate that PKC acts on an exocytotic mechanism other than Ca2+ influx, buffering and removal. The results of this paper indicate that this is indeed the case. In order to further elucidate the underlying mechanism of PKC-dependent modulation of exocytosis, the effect of [Ca2+]o on PKC-dependent potentiation, the effect of PKC on the recovery rate of EPSCs from depression after a high frequency train of stimuli, and the correlation between the EPSC potentiation and steady-state EPSC during a train were investigated. The present results exclude the notion that PKC upregulates the size of the readily releasable pool or the number of release sites. It is suggested that PKC upregulates the Ca2+ sensitivity of the process that controls the exocytotic fusion probability.
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noradrenaline modulates transmitter release by enhancing the ca2 sensitivity of exocytosis in the chick ciliary Presynaptic Terminal
The Journal of Physiology, 1996Co-Authors: Hiromu YawoAbstract:1. The giant Presynaptic Terminal of chick ciliary ganglion was used to examine how noradrenaline (NA) modulates neurotransmitter release. The cholinergic excitatory postsynaptic currents (EPSCs) were recorded under whole-cell voltage clamp of the postsynaptic neuron. 2. Although the EPSC was potentiated by NA, the current directly activated by acetylcholine (IACh) was unaffected. NA also increased the quantal contents without changing the quantal size. 3. The NA-dependent potentiation was antagonized by neither phentolamine nor propranolol. The EPSC was also potentiated by adrenaline and dopamine but not by normetanephrine, phenylephrine or isoprenaline. The EPSC was attenuated by clonidine. Therefore, NA potentiated the transmitter release through a receptor pharmacologically different from both alpha- and beta-adrenergic receptors. 4. The Ca2+ increment produced by an action potential (delta[Ca2+]pre) was reduced by NA through an alpha 2-adrenergic receptor. However, when alpha 2-adrenergic receptors were blocked, neither delta[Ca2+]pre nor resting Ca2+ were changed by NA. 5. The [Ca2+]o-EPSC relation was shifted by NA, decreasing the half-saturating [Ca2+]o, without changing the maximum. 6. It is concluded that NA-dependent potentiation of transmitter release was due to an increase in the Ca2+ sensitivity of the exocytotic process. The enhancement of the fusion probability is suggested.
Nao Chuhma - One of the best experts on this subject based on the ideXlab platform.
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differential development of ca2 dynamics in Presynaptic Terminal and postsynaptic neuron of the rat auditory synapse
Brain Research, 2001Co-Authors: Nao Chuhma, Harunori OhmoriAbstract:Abstract Postnatal development of Ca 2+ influx and Ca 2+ clearance capacity were investigated in the synapse of medial nucleus of the trapezoid body (MNTB) of rat with fura-2 fluorimetry. In contrast to the Presynaptic Terminal, Ca 2+ dynamics does not basically change in the postsynaptic principal neuron developmentally. This differential development of Ca 2+ dynamics between pre- and postsynaptic neurons might be crucial for the organized formation and functional maturation of this synapse.
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Synchronisation of neurotransmitter release during postnatal development in a calyceal Presynaptic Terminal of rat
The Journal of Physiology, 2001Co-Authors: Nao Chuhma, Konomi Koyano, Harunori OhmoriAbstract:Mechanisms contributing to the synchronisation of transmitter release during development were studied in synapses of the medial nucleus of the trapezoid body (MNTB) using patch recording and Ca2+ imaging techniques in a rat brainstem slice preparation. Excitatory postsynaptic currents (EPSCs) were generated in an all-or-none manner at immature synapses (postnatal days earlier than P6). Many delayed miniature EPSC (mEPSC)-like currents followed EPSCs at immature synapses, while observations of delayed mEPSC-like currents were rare at mature synapses (later than P9). At immature synapses bath application of either omega-conotoxin GVIA or omega-agatoxin-IVA reduced EPSCs (both to 40% of control), and Ca2+ currents in the Presynaptic Terminal (both to 70% of control). The frequency of delayed mEPSC-like currents was reduced by omega-conotoxin GVIA, but not by omega-agatoxin IVA. At immature synapses delayed mEPSC-like currents were rare after incubation of the slice with extrinsic Ca2+ buffers (EGTA AM). At mature synapses many mEPSC-like currents followed evoked EPSCs after partial block of Ca2+ channels by bath application of a low concentration of Cd2+ (3 microM) or omega-agatoxin IVA (50 nM) but not by low [Ca2+]o (0.5-1 mM). Ca2+ transients induced by action potentials in Presynaptic Terminals were monitored by adding a high concentration of fura-2 (200 microM) to the pipette. Their decay time course was slower at immature Presynaptic Terminals than at mature Terminals. Both the Ca2+ extrusion rate and the endogenous Ca2+ binding capacity were estimated to be smaller at immature Terminals than at mature Terminals. These results suggest that the maturation of synaptic transmission in MNTB progresses with the capacity for Ca2+ clearance from the Presynaptic Terminal. The possible importance of developmental increases in both Ca2+ clearance capacity and Ca2+ currents is discussed in relation to the synchronisation of transmitter release.
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omega conotoxin sensitive and resistant transmitter release from the chick ciliary Presynaptic Terminal
The Journal of Physiology, 1994Co-Authors: Hiromu Yawo, Nao ChuhmaAbstract:1. Synaptically evoked responses to stimulation of the oculomotor nerve were recorded from the ciliary nerve in chick embryos. The postsynaptic currents in response to Presynaptic stimulation (EPSCs) were also recorded under whole-cell voltage clamp of the ciliary cell. 2. The ciliary nerve response was dependent on the extracellular Ca2+ concentration ([Ca2+]o). omega-Conotoxin GVIA (omega-CgTX, 100 nM) increased the [Ca2+]o necessary to evoke the half-maximal response by a factor of 1.7 without changing the slope of [Ca2+]o dependence. Dihydropyridine (DHP) derivatives, nifedipine or Bay K 8644, did not affect the [Ca2+]o sensitivity of ciliary nerve response. 3. The EPSC was usually preceded by the capacitive coupling response of the Presynaptic action potential. In some records, the EPSCs were also preceded by the electrical coupling responses which were the mirror images of the Presynaptic action potentials. The current-voltage relation of the EPSCs showed inward rectification. 4. The EPSC was potentiated by 4-aminopyridine (4-AP) as a result of prolongation of the falling phase of Presynaptic action potential. In the presence of high [Ca2+]o and 4-AP, a small fraction of EPSC was resistant to omega-CgTX. 5. The resting potential of the Presynaptic Terminal was changed from -69 to -57 mV by increasing [K+]o from 1 to 10 mM. The same procedure decreased the omega-CgTX-resistant EPSC by 30%, whereas the omega-CgTX-untreated EPSC in low-Ca2+ saline was not affected by the change in [K+]o. 6. The nerve-evoked increase in intracellular Ca2+ was recorded from the Presynaptic Terminal (delta[Ca2+]pre). The delta[Ca2+]pre was larger in a solution containing 10 mM Ca2+ and 1 mM K+ after treating with omega-CgTX than in a solution containing 2 mM Ca2+ and 16 mM Mg2+ before treating with omega-CgTX. The EPSC was, in contrast, smaller in the 10 mM Ca(2+)-1 mM K+ solution after omega-CgTX treatment than in the 2 mM Ca(2+)-16 mM Mg2+ solution before omega-CgTX treatment. 7. Similarly, the EPSC was smaller in the 10 mM Ca(2+)-1 mM K+ solution containing 5 microM La3+ than in the 2 mM Ca(2+)-16 mM Mg2+ solution, whereas the delta [Ca2+]pre was larger in the 10 mM Ca(2+)-1 mM K+ solution containing 5 micrograms La3+ than in the 2 mM Ca(2+)-16 mM Mg2+ solution. 8. It is concluded that the omega-CgTX-sensitive Ca2+ conductance of the Presynaptic Terminal is the principal source of Ca2+ involved in transmitter release.(ABSTRACT TRUNCATED AT 400 WORDS)
Yishi Jin - One of the best experts on this subject based on the ideXlab platform.
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Presynaptic Terminal Differentiation: Transport and Assembly
Current opinion in neurobiology, 2004Co-Authors: Mei Zhen, Yishi JinAbstract:The formation of chemical synapses involves reciprocal induction and independent assembly of pre- and postsynaptic structures. The major events in Presynaptic Terminal differentiation are the formation of the active zone and the clustering of synaptic vesicles. A number of proteins that are present in the Presynaptic active zone have been identified. Recent studies of various mutants have clarified the in vivo functions of some of the main players. Time-lapse imaging studies have captured dynamic and transient events in the transport of synaptic components, and therefore provided insight into the early stages of synaptogenesis.
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Regulation of Presynaptic Terminal organization by C. elegans RPM-1, a putative guanine nucleotide exchanger with a RING-H2 finger domain.
Neuron, 2000Co-Authors: Mei Zhen, Xun Huang, Bruce A. Bamber, Yishi JinAbstract:Presynaptic Terminals contain highly organized subcellular structures to facilitate neurotransmitter release. In C. elegans, the typical Presynaptic Terminal has an electron-dense active zone surrounded by synaptic vesicles. Loss-of-function mutations in the rpm-1 gene result in abnormally structured Presynaptic Terminals in GABAergic neuromuscular junctions (NMJs), most often manifested as a single Presynaptic Terminal containing multiple active zones. The RPM-1 protein has an RCC1-like guanine nucleotide exchange factor (GEF) domain and a RING-H2 finger. RPM-1 is most similar to the Drosophila Presynaptic protein Highwire (HIW) and the mammalian Myc binding protein Pam. RPM-1 is localized to the Presynaptic region independent of synaptic vesicles and functions cell autonomously. The temperature-sensitive period of rpm-1 coincides with the time of synaptogenesis. rpm-1 may regulate the spatial arrangement, or restrict the formation, of Presynaptic structures.
Mei Zhen - One of the best experts on this subject based on the ideXlab platform.
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Presynaptic Terminal Differentiation
Protein Trafficking in Neurons, 2007Co-Authors: Mei ZhenAbstract:Publisher Summary A majority of the communication in the nervous system is mediated by chemical synapses. Therefore, synapse formation is essential for the establishment of neural circuits that are responsible for physical and cognitive functions. Identifying molecular mechanisms that underlie synapse development provides a key insight into normal development and the potential cause for the onset of mental illness. Protein components of chemical synapses have been identified in both vertebrate and invertebrate nervous systems. Many common and conserved components have been discovered. This convergence provides a strong basis for guided cross-examination of the functional conservation among components of vertebrate and invertebrate synapses. It also serves as a tool to help unravel common molecular mechanisms that govern synapse development and, in addition, allows a comparison of the difference between vertebrate and invertebrate synapse development and function. This chapter focuses on the mechanisms that regulate two aspects of Presynaptic Terminal differentiation in vertebrates and invertebrates: active zone assembly and Presynaptic growth. The chapter also provides a future perspective on how to bridge the knowledge obtained from vertebrate and invertebrate synapses through various experimental approaches.
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Presynaptic Terminal Differentiation: Transport and Assembly
Current opinion in neurobiology, 2004Co-Authors: Mei Zhen, Yishi JinAbstract:The formation of chemical synapses involves reciprocal induction and independent assembly of pre- and postsynaptic structures. The major events in Presynaptic Terminal differentiation are the formation of the active zone and the clustering of synaptic vesicles. A number of proteins that are present in the Presynaptic active zone have been identified. Recent studies of various mutants have clarified the in vivo functions of some of the main players. Time-lapse imaging studies have captured dynamic and transient events in the transport of synaptic components, and therefore provided insight into the early stages of synaptogenesis.
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Regulation of Presynaptic Terminal organization by C. elegans RPM-1, a putative guanine nucleotide exchanger with a RING-H2 finger domain.
Neuron, 2000Co-Authors: Mei Zhen, Xun Huang, Bruce A. Bamber, Yishi JinAbstract:Presynaptic Terminals contain highly organized subcellular structures to facilitate neurotransmitter release. In C. elegans, the typical Presynaptic Terminal has an electron-dense active zone surrounded by synaptic vesicles. Loss-of-function mutations in the rpm-1 gene result in abnormally structured Presynaptic Terminals in GABAergic neuromuscular junctions (NMJs), most often manifested as a single Presynaptic Terminal containing multiple active zones. The RPM-1 protein has an RCC1-like guanine nucleotide exchange factor (GEF) domain and a RING-H2 finger. RPM-1 is most similar to the Drosophila Presynaptic protein Highwire (HIW) and the mammalian Myc binding protein Pam. RPM-1 is localized to the Presynaptic region independent of synaptic vesicles and functions cell autonomously. The temperature-sensitive period of rpm-1 coincides with the time of synaptogenesis. rpm-1 may regulate the spatial arrangement, or restrict the formation, of Presynaptic structures.
