scholarly journals Computational modeling predicts acidic microdomains in the glutamatergic synaptic cleft

2021 ◽  
Author(s):  
Touhid Feghhi ◽  
Roberto X Hernandez ◽  
Michal Stawarski ◽  
Connon I Thomas ◽  
Naomi Kamasawa ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Time Course ◽  
Small Volume ◽  
Reaction Diffusion ◽  
Synaptic Cleft ◽  
Structural Features ◽  
Glutamatergic Synapses ◽  
Diffusion Scheme ◽  
Chemical Synapses ◽  
Ph Probes

At chemical synapses, synaptic vesicles release their acidic contents into the cleft leading to the expectation that the cleft should acidify. However, fluorescent pH probes targeted to the cleft of conventional glutamatergic synapses in both fruit flies and mice reveal cleft alkalinization, rather than acidification. Here, using a reaction-diffusion scheme, we modeled pH dynamics at the Drosophila neuromuscular junction (NMJ) as glutamate, adenosine triphosphate (ATP) and protons (H+) are released into the cleft. The model incorporates bicarbonate and phosphate buffering systems as well as plasma membrane calcium-ATPase (PMCA) activity and predicts substantial cleft acidification but only for fractions of a millisecond following neurotransmitter release. Thereafter, the cleft rapidly alkalinizes and remains alkaline for over 100 milliseconds, as the PMCA removes H+ from the cleft in exchange for calcium ions (Ca2+) from adjacent pre- and post-synaptic compartments; thus recapitulating the empirical data. The extent of synaptic vesicle loading and time course of exocytosis has little influence on the magnitude of acidification. Phosphate, but not bicarbonate buffering is effective at ameliorating the magnitude and time course of the acid spike, while both buffering systems are effective at ameliorating cleft alkalinization. The small volume of the cleft levies a powerful influence on the magnitude of alkalinization and its time course. Structural features that open the cleft to adjacent spaces appear to be essential for alleviating the extent of pH disturbances accompanying neurotransmission.

scholarly journals The Fine Structure of Synapses in the Ciliary Ganglion of the Chick

1960 ◽  
Vol 7 (1) ◽  
pp. 31-36 ◽  
Author(s):  
A. J. de Lorenzo
Keyword(s):  
Fine Structure ◽  
Synaptic Vesicles ◽  
Ganglion Cells ◽  
Single Cells ◽  
Synaptic Cleft ◽  
Structural Features ◽  
Ciliary Ganglion ◽  
Single Axon ◽  
Electron Microscopes ◽  
Electron Microscope Image

Ciliary ganglia of chick embryos and newly hatched chicks were examined in the light and electron microscopes. Particular attention was given to the fine structure of calyciform synapses, which are characteristically found in ciliary ganglia of birds. The calyciform endings are characterized by large expansions of the presynaptic axons upon ganglion cells, and the terminal processes extend over a considerable area of the cell surface. Often, indeed they appear to envelop the cell. In the electron microscope image, the appositional membranes are separated by a space about 300 to 400 A wide; i.e., the synaptic cleft. At irregularly spaced regions, the appositional membranes show areas of increased density. The presynaptic processes contain clusters of synaptic vesicles, localized at these dense regions. Thus the fine structure complex typical of other synapses is evident. The unique structural features of this synapse are as follows: (a) The calyx or presynaptic terminal derives from a single axon, does not arborize, and terminates upon a single ganglion cell. Thus, unlike the classical bouton terminal, this represents an anatomical device for firing single cells by single axons. (b) The surface area in contiguity, i.e., the area of appositional membranes, is far more extensive than the bouton terminal. The fine structure of this synapse is compared with others, for example, the classical boutons terminaux and purely electrical synapses, in an attempt to correlate fine structure with function.

The uptake inhibitor L-trans-PDC enhances responses to glutamate but fails to alter the kinetics of excitatory synaptic currents in the hippocampus

1993 ◽  
Vol 70 (5) ◽  
pp. 2187-2191 ◽  
Author(s):  
J. S. Isaacson ◽  
R. A. Nicoll
Keyword(s):  
Time Course ◽  
Glutamate Uptake ◽  
Hippocampal Slices ◽  
Synaptic Cleft ◽  
Gamma Aminobutyric Acid ◽  
Patch Clamp Recording ◽  
Glutamatergic Synapses ◽  
Synaptic Currents ◽  
Ca1 Region ◽  
Transmitter Uptake

1. We have used patch-clamp recording techniques to study the physiological properties of a recently described glutamate uptake blocker, L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC), in the CA1 region of the guinea pig hippocampus. 2. L-trans-PDC markedly potentiated the action of exogenously applied glutamate and raised the ambient extracellular levels of glutamate in hippocampal slices. Despite these actions, L-trans-PDC did not affect the time course of either the N-methyl-D-aspartate (NMDA) or non-NMDA receptor-mediated synaptic currents evoked by the stimulation of a large number of neighboring synapses. 3. These findings are consistent with models of fast synaptic transmission in which transmitter is rapidly cleared from the synaptic cleft by diffusion. However, in marked contrast to fast gamma-aminobutyric acid A (GABAA) synapses in the hippocampus, uptake does not appear to play a role in regulating the "spill-over" of transmitter from neighboring, co-activated glutamatergic synapses. Therefore, either diffusion alone can effectively limit the temporal and spatial domain of synaptically released glutamate, or alternatively, L-trans-PDC like other currently available blockers is not sufficiently potent to reveal a role for transmitter uptake at glutamatergic synapses.

Restoring synaptic vesicles during compensatory endocytosis

2015 ◽  
Vol 57 ◽  
pp. 121-134 ◽  
Author(s):  
Anne Gauthier-Kemper ◽  
Martin Kahms ◽  
Jürgen Klingauf
Keyword(s):  
Self Assembly ◽  
Synaptic Vesicles ◽  
Molecular Level ◽  
Synaptic Cleft ◽  
Electrical Signal ◽  
Presynaptic Site ◽  
Postsynaptic Site ◽  
Protein Complement ◽  
Chemical Synapses ◽  
Activate Receptor

In the CNS (central nervous system), nerve cells communicate by transmitting signals from one to the next across chemical synapses. Electrical signals trigger controlled secretion of neurotransmitter by exocytosis of SV (synaptic vesicles) at the presynaptic site. Neurotransmitters diffuse across the synaptic cleft, activate receptor channels in the receiving neuron at the postsynaptic site, and thereby elicit a new electrical signal. Repetitive stimulation should result in fast depletion of fusion-competent SVs, given their limited number in the presynaptic bouton. Therefore, to support repeated rounds of release, a fast trafficking cycle is required that couples exocytosis and compensatory endocytosis. During this exo-endocytic cycle, a defined stoichiometry of SV proteins has to be preserved, that is, membrane proteins have to be sorted precisely. However, how this sorting is accomplished on a molecular level is poorly understood. In the present chapter we review recent findings regarding the molecular composition of SVs and the mechanisms that sort SV proteins during compensatory endocytosis. We identify self-assembly of SV components and individual cargo recognition by sorting adaptors as major mechanisms for maintenance of the SV protein complement.

Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

1990 ◽  
Vol 48 (3) ◽  
pp. 398-399
Author(s):  
A.M. Andrews ◽  
S.W. Wilson ◽  
A.C. Scallet ◽  
S.F. Ali ◽  
J. Bailey ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
Inhalation Exposure ◽  
Synaptic Cleft ◽  
High Dose ◽  
Withdrawal Time ◽  
Treatment Groups ◽  
Ultrastructural Evidence ◽  
Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

Opponent vesicular transporters regulate the strength of glutamatergic neurotransmission in a C. elegans sensory circuit

2021 ◽  
Author(s):  
Jung-Hwan Choi ◽  
Lauren Bayer Horowitz ◽  
Niels Ringstad
Keyword(s):  
Synaptic Vesicles ◽  
Glutamate Release ◽  
Glutamate Transporter ◽  
Synaptic Function ◽  
Functional Coupling ◽  
Glutamate Signaling ◽  
C Elegans ◽  
Vesicular Transporters ◽  
Chemical Synapses

At chemical synapses, neurotransmitters are packaged into synaptic vesicles that release their contents in response to depolarization. Despite its central role in synaptic function, regulation of the machinery that loads vesicles with neurotransmitters remains poorly understood. We find that synaptic glutamate signaling in a C. elegans chemosensory circuit is regulated by antagonistic interactions between the canonical vesicular glutamate transporter EAT-4/VGLUT and another vesicular transporter, VST-1. Loss of VST-1 strongly potentiates glutamate release from chemosensory BAG neurons and disrupts chemotaxis behavior. Analysis of the circuitry downstream of BAG neurons shows that excess glutamate release disrupts behavior by inappropriately recruiting RIA interneurons to the BAG-associated chemotaxis circuit. Our data indicate that in vivo the strength of glutamatergic synapses is controlled by regulation of neurotransmitter packaging into synaptic vesicles via functional coupling of VGLUT and VST-1.

Rapidly Deactivating AMPA Receptors Determine Excitatory Synaptic Transmission to Interneurons in the Nucleus Tractus Solitarius From Rat

1997 ◽  
Vol 78 (1) ◽  
pp. 82-91 ◽  
Author(s):  
Stefan Titz ◽  
Bernhard U. Keller
Keyword(s):  
Synaptic Transmission ◽  
Ampa Receptor ◽  
Decay Time ◽  
Ampa Receptors ◽  
Time Course ◽  
Nucleus Tractus Solitarius ◽  
Synaptic Cleft ◽  
Excitatory Synaptic Transmission ◽  
Membrane Properties ◽  
Time Constants

Titz, Stefan and Bernhard U. Keller. Rapidly deactivating AMPA receptors determine excitatory synaptic transmission to interneurons in the nucleus tractus solitarius from rat. J. Neurophysiol. 78: 82–91, 1997. Excitatory synaptic transmission was investigated in interneurons of the parvocellular nucleus tractus solitarius (pNTS) by performing patch-clamp experiments in thin slice preparations from rat brain stem. Stimulation of single afferent fibers evoked excitatory postsynaptic currents (EPSCs) mediated by glutamate receptors of the dl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) and N-methyl-d-aspartate types. AMPA-receptor-mediated EPSCs displayed decay time constants of 3.5 ± 1.2 (SD) ms (13 cells), which were slow compared with EPSC decay time constants in neurons of the cerebellum or hippocampus. Slow EPSC decay was not explained by dendritic filtering, because the passive membrane properties of pNTS interneurons provided favorable voltage-clamp conditions. Also, the slowness of EPSC decay did not result from slow deactivation of AMPA receptors (0.7 ± 0.2 ms, 5 cells), which was investigated during rapid application of agonist to outside-out patches. Comparison of AMPA receptor kinetics with EPSC decay time constants suggested that the slow time course of EPSCs resulted from the prolonged presence of glutamate in the synaptic cleft.

scholarly journals Opponent vesicular transporters regulate the strength of glutamatergic neurotransmission in a C. elegans sensory circuit

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jung-Hwan Choi ◽  
Lauren Bayer Horowitz ◽  
Niels Ringstad
Keyword(s):  
Synaptic Vesicles ◽  
Glutamate Release ◽  
Glutamate Transporter ◽  
Synaptic Function ◽  
Functional Coupling ◽  
Glutamate Signaling ◽  
C Elegans ◽  
Vesicular Transporters ◽  
Chemical Synapses

AbstractAt chemical synapses, neurotransmitters are packaged into synaptic vesicles that release their contents in response to depolarization. Despite its central role in synaptic function, regulation of the machinery that loads vesicles with neurotransmitters remains poorly understood. We find that synaptic glutamate signaling in a C. elegans chemosensory circuit is regulated by antagonistic interactions between the canonical vesicular glutamate transporter EAT-4/VGLUT and another vesicular transporter, VST-1. Loss of VST-1 strongly potentiates glutamate release from chemosensory BAG neurons and disrupts chemotaxis behavior. Analysis of the circuitry downstream of BAG neurons shows that excess glutamate release disrupts behavior by inappropriately recruiting RIA interneurons to the BAG-associated chemotaxis circuit. Our data indicate that in vivo the strength of glutamatergic synapses is controlled by regulation of neurotransmitter packaging into synaptic vesicles via functional coupling of VGLUT and VST-1.

Time-Course Studies of Phytoalexins and Glucosinolates in UV-Irradiated Turnip Tissue

1991 ◽  
Vol 46 (3-4) ◽  
pp. 189-193 ◽  
Author(s):  
Kenji Monde ◽  
Mitsuo Takasugi ◽  
Jenny A. Lewis ◽  
G. Roger Fenwick
Keyword(s):  
High Performance ◽  
Time Course ◽  
Brassica Campestris ◽  
Structural Features ◽  
Biologically Active ◽  
Indole Glucosinolates ◽  
Freeze Dried ◽  
Indole Phytoalexins ◽  
The Individual ◽  
Complex Manner

Sliced turnip root (Brassica campestris L. ssp rapa) was irradiated for a total of 20 min with a 15 W germicidal lamp and the tissue incubated at 25 °C. The effects of such treatment on indole phytoalexins (methoxybrassinin (I); brassinin (II); cyclobrassinin (III); spirobrassinin (IV) and glucosinolates were determined using high performance liquid chromatography procedures. Accumulation of phytoalexins I - III was evident within 8 h of irradiation, whilst formation of spirobrassinin was evident only after 24 h. Maximal levels of III and IV (> 100 μg g-1 freeze dried tissue) were greater than those of I and II (27 and 17 μg g-1, respectively). The individual glucosinolate levels were affected in a complex manner; whilst most glucoinolates decreased on storage, the levels of indole glucosinolates, glucobrassicin (XI) and 1-methoxyglucobrassicin (XIII), increased until 5 to 6 days after irradiation and thereafter declined. Whilst structural features of I - IV , XI and XIII suggest close biosynthetic relationships between these classes of biologically-active indoles, further studies are needed to establish this point unambiguously.

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