Retrograde regulation of synaptic vesicle endocytosis and recycling (original) (raw)
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The Journal of Neuroscience, 2003
Postsynaptic alterations are currently believed to be able to fully account for NMDA-receptor-dependent long-term depression (LTD) and long-term potentiation of synaptic strength, although there is also evidence supporting changes in presynaptic release. Using dualphoton laser scan microscopy of N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide (FM1-43) to directly visualize presynaptic vesicular release at Schaffer collateral-CA1 excitatory synapses in hippocampal slices, we demonstrate reduced vesicular release associated with LTD. Selective loading, by hypertonic shock, of the readily releasable vesicle pool (RRP) showed that LTD of release is a selective modification of release from the RRP. Presynaptic LTD of RRP release required activation of NMDA receptors, production and extracellular diffusion of the intercellular messenger NO, and activation of cGMP-dependent protein kinase.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
Postsynaptic alterations are currently believed to be able to fully account for NMDA-receptor-dependent long-term depression (LTD) and long-term potentiation of synaptic strength, although there is also evidence supporting changes in presynaptic release. Using dualphoton laser scan microscopy of N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide (FM1-43) to directly visualize presynaptic vesicular release at Schaffer collateral-CA1 excitatory synapses in hippocampal slices, we demonstrate reduced vesicular release associated with LTD. Selective loading, by hypertonic shock, of the readily releasable vesicle pool (RRP) showed that LTD of release is a selective modification of release from the RRP. Presynaptic LTD of RRP release required activation of NMDA receptors, production and extracellular diffusion of the intercellular messenger NO, and activation of cGMP-dependent protein kinase.
The Journal of Physiology, 2012
• Presynaptic terminals in hippocampal neurons are characterized by two functionally defined vesicle populations: a recycling pool, which supports activity-evoked neurotransmission, and a resting pool. • Between individual synapses, the relative proportions of these two pools are highly variable, suggesting that this parameter might be specifically regulated to support changes in synaptic efficacy. • Using fluorescence imaging and correlative ultrastructural approaches we show here that a form of synaptic potentiation dependent on N -methyl-D-aspartic acid (NMDA) receptor activity can lead to a rapid and sustained expansion of the recycling fraction at the expense of the resting pool. • This recruitment of vesicles depends on nitric oxide signalling and calcineurin activity, and is accompanied by an increase in synaptic release probability. • We suggest that vesicle exchange between these pools provides a rapid mechanism to support adjustments in synaptic strength associated with a form of Hebbian plasticity.
Nature communications, 2018
NMDA receptors (NMDARs) are crucial for excitatory synaptic transmission and synaptic plasticity. The number and subunit composition of synaptic NMDARs are tightly controlled by neuronal activity and sensory experience, but the molecular mechanism mediating NMDAR trafficking remains poorly understood. Here, we report that RIM1, with a well-established role in presynaptic vesicle release, also localizes postsynaptically in the mouse hippocampus. Postsynaptic RIM1 in hippocampal CA1 region is required for basal NMDAR-, but not AMPA receptor (AMPAR)-, mediated synaptic responses, and contributes to synaptic plasticity and hippocampus-dependent memory. Moreover, RIM1 levels in hippocampal neurons influence both the constitutive and regulated NMDAR trafficking, without affecting constitutive AMPAR trafficking. We further demonstrate that RIM1 binds to Rab11 via its N terminus, and knockdown of RIM1 impairs membrane insertion of Rab11-positive recycling endosomes containing NMDARs. Togeth...
Nitric oxide stimulates Ca2+-independent synaptic vesicle release
Neuron, 1994
A new fluorescence method using the dye FM1-43 was used to examine exocytotic release from hippocampal synaptosomes. Nitric oxide caused a marked transient stimulation of vesicle release. Several structurally unrelated d nitric oxide donors, sodium nitroprusside, Snitroso-N-acetylpenicillamine, 3-morpholino-sydnonimine, and acidified sodium nitrite, were effective. Release stimulated by nitric oxide and KCI were comparable in time course, using both the fluorescence assay and [3H]~glutamate to monitor neurotransmitter release. Activation of guanylyl cyclase was not responsible for nitric oxide-stimulated release. Unlike release stimulated by KCI or A23187, nitric oxide-stimulated release was found to be independent of a rise in intrasynaptosomal Ca*+. Indo-l/AM measurements indicated that nitric oxide actually decreased intracellular Ca*+, and the Ca*+ channel blocker Cd*+ did not affect nitric oxide-stimulated vesicle release. Nitric oxide does, however, appear to act on the Ca*+-sensitive pool of vesicles. Nitric oxide may be the first physiological mediator that induces vesicle exocytosis without raising Ca*+ and may provide an interesting new tool for the study of molecules involved in vesicle exocytosis.
Neurotransmitter release and synaptic vesicle recycling
Neuroscience, 1990
Precise timing between vesicle fusion and quanta1 release 2.2. Correlation between quanta1 release and changes in vesicle population THE MECHANISM(S) OF RECYCLING 3.1. Membrane recycling and quanta1 turnover 3.2. The recovery of vesicle membrane from the axolemma 3.3. Tracing of vesicle membrane components during recycling REGULATION OF QUANTAL RELEASE 4.1. Ca*+ and other possible regulatory agents 4.2. The possible regulatory role of cytoskeletal components 4.3. Coexistence of multiple pathways of exocytosis
Nitric Oxide-Mediated Posttranslational Modifications: Impacts at the Synapse
Oxidative Medicine and Cellular Longevity, 2016
Nitric oxide (NO) is an important gasotransmitter molecule that is involved in numerous physiological processes throughout the nervous system. In addition to its involvement in physiological plasticity processes (long-term potentiation, LTP; long-term depression, LTD) which can include NMDAR-mediated calcium-dependent activation of neuronal nitric oxide synthase (nNOS), new insights into physiological and pathological consequences of nitrergic signalling have recently emerged. In addition to the canonical cGMP-mediated signalling, NO is also implicated in numerous pathways involving posttranslational modifications. In this review we discuss the multiple effects of S-nitrosylation and 3-nitrotyrosination on proteins with potential modulation of function but limit the analyses to signalling involved in synaptic transmission and vesicular release. Here, crucial proteins which mediate synaptic transmission can undergo posttranslational modifications with either pre- or postsynaptic orig...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014
From the early periods of neurogenesis and migration, up until synaptogenesis, both nitric oxide (NO) and its downstream messenger, cGMP, are thought to influence the development of neurons. The NO/cGMP/cGMP-dependent protein kinase (cGK) pathway regulates the clustering and recruitment of synaptic proteins and vesicles to the synapse, adjusting the exoendocytic cycle to the intensity of activity and accelerating endocytosis following large-scale exocytosis. Here, we show that blockage of the N-methyl-D-aspartate receptor impairs the cycling of synaptic vesicles in a subset of boutons on cerebellar granule cells, an effect that was reversed by increasing cGMP. Furthermore, we demonstrate that presynaptic cGK type II (cGKII) plays a major role in this process. Using the FM1-43 dye to track vesicle recycling, we found that knockdown of cGKII and/or the application of a cGK inhibitor reduced the efficiency of synaptic vesicle recycling to a similar extent. Likewise, in cerebellar granu...
Molecular Brain Research, 2001
In brain synapses, nitric oxide synthase activation is coupled to N-methyl-D-aspartate-mediated calcium entry at postsynaptic densities through regulatory protein complexes, however a presynaptic equivalent to this signaling mechanism has not yet been identified. Novel evidence indicates that N-methyl-D-aspartate glutamate receptors may play a presynaptic role in synaptic plasticity. Thus, we investigated whether ionotropic glutamate receptor activation in isolated nerve terminals regulates neurotransmitter release, through nitric oxide formation. N-Methyl-D-aspartate dose-dependently inhibited the release of glutamate evoked by 4-aminopyridine (IC 5155 mM), and 50 this effect was reversed by the N-methyl-D-aspartate receptor antagonist D-(2)-2-amino-5-phosphopentanoic acid and by the nitric oxide synthase inhibitor, L-nitroarginine, in synaptosomes isolated from whole hippocampus, CA3 and CA1 areas, but not from the dentate gyrus. In contrast, the 4-aminopyridine-evoked release of glutamate was reduced by a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or kainate by a nitric oxide-independent mechanism, since it was not blocked by L-nitroarginine, and N-methyl-D-aspartate, but not a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or kainate, significantly increased cGMP formation. Presynaptic N-methyl-Daspartate receptors are probably involved since removing extracellular nitric oxide with the scavenger 2-(4-carboxyphenyl)-4,4,5,5tetramethylimidazoline-1-oxyl 3-oxide did not block the depression of glutamate release by N-methyl-D-aspartate. The mechanism underlying this depression involves the inhibition of synaptic vesicle exocytosis since N-methyl-D-aspartate / nitric oxide inhibited the 3 1 4 release of [ H]glutamate and [ C]GABA evoked by hypertonic sucrose. The results also suggest that presynaptic N-methyl-D-aspartate receptors may function as auto-and heteroreceptors.