Transmitter Metabolism as a Mechanism of Synaptic Plasticity: A Modeling Study

2004 ◽  
Vol 91 (1) ◽  
pp. 25-39 ◽  
Author(s):  
Nikolai Axmacher ◽  
Martin Stemmler ◽  
Dominique Engel ◽  
Andreas Draguhn ◽  
Raphael Ritz
Keyword(s):  
Nervous System ◽  
Synaptic Plasticity ◽  
Transmitter Release ◽  
A Priori ◽  
Presynaptic Terminal ◽  
Synaptic Efficacy ◽  
Specific Mechanism ◽  
Presynaptic Function ◽  
Presynaptic Vesicle ◽  
Vesicle Cycle

The nervous system adapts to experience by changes in synaptic strength. The mechanisms of synaptic plasticity include changes in the probability of transmitter release and in postsynaptic responsiveness. Experimental and neuropharmacological evidence points toward a third variable in synaptic efficacy: changes in presynaptic transmitter concentration. Several groups, including our own, have reported changes in the amplitude and frequency of postsynaptic (miniature) events indicating that alterations in transmitter content cause alterations in vesicular transmitter content and vesicle dynamics. It is, however, not a priori clear how transmitter metabolism will affect vesicular transmitter content and how this in turn will affect pre- and postsynaptic functions. We therefore have constructed a model of the presynaptic terminal incorporating vesicular transmitter loading and the presynaptic vesicle cycle. We hypothesize that the experimentally observed synaptic plasticity after changes in transmitter metabolism puts predictable restrictions on vesicle loading, cytoplasmic–vesicular transmitter concentration gradient, and on vesicular cycling or release. The results of our model depend on the specific mechanism linking presynaptic transmitter concentration to vesicular dynamics, that is, alteration of vesicle maturation or alteration of release. It also makes a difference whether differentially filled vesicles are detected and differentially processed within the terminal or whether vesicle filling acts back onto the terminal by presynaptic autoreceptors. Therefore, the model allows one to decide, at a given synapse, how transmitter metabolism is linked to presynaptic function and efficacy.

scholarly journals The Function of Selenium in Central Nervous System: Lessons from MsrB1 Knockout Mouse Models

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1372
Author(s):  
Tengrui Shi ◽  
Jianxi Song ◽  
Guanying You ◽  
Yujie Yang ◽  
Qiong Liu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Knockout Mouse Model ◽  
The Central Nervous System

MsrB1 used to be named selenoprotein R, for it was first identified as a selenocysteine containing protein by searching for the selenocysteine insert sequence (SECIS) in the human genome. Later, it was found that MsrB1 is homologous to PilB in Neisseria gonorrhoeae, which is a methionine sulfoxide reductase (Msr), specifically reducing L-methionine sulfoxide (L-Met-O) in proteins. In humans and mice, four members constitute the Msr family, which are MsrA, MsrB1, MsrB2, and MsrB3. MsrA can reduce free or protein-containing L-Met-O (S), whereas MsrBs can only function on the L-Met-O (R) epimer in proteins. Though there are isomerases existent that could transfer L-Met-O (S) to L-Met-O (R) and vice-versa, the loss of Msr individually results in different phenotypes in mice models. These observations indicate that the function of one Msr cannot be totally complemented by another. Among the mammalian Msrs, MsrB1 is the only selenocysteine-containing protein, and we recently found that loss of MsrB1 perturbs the synaptic plasticity in mice, along with the astrogliosis in their brains. In this review, we summarized the effects resulting from Msr deficiency and the bioactivity of selenium in the central nervous system, especially those that we learned from the MsrB1 knockout mouse model. We hope it will be helpful in better understanding how the trace element selenium participates in the reduction of L-Met-O and becomes involved in neurobiology.

scholarly journals A Discrete Presynaptic Vesicle Cycle for Neuromodulator Receptors

Neuron ◽  
2020 ◽  
Vol 105 (4) ◽  
pp. 663-677.e8 ◽  
Author(s):  
Damien Jullié ◽  
Miriam Stoeber ◽  
Jean-Baptiste Sibarita ◽  
Hanna L. Zieger ◽  
Thomas M. Bartol ◽  
...  
Keyword(s):  
Presynaptic Vesicle ◽  
Vesicle Cycle

Problems associated with the use of tetraethylammonium to test for monosynaptic connexions

1975 ◽  
Vol 62 (3) ◽  
pp. 797-803
Author(s):  
M. S. Berry ◽  
V. W. Pentreath
Keyword(s):  
Nervous System ◽  
Transmitter Release ◽  
Gastropod Mollusc ◽  
Postsynaptic Response ◽  
Postsynaptic Potential ◽  
Planorbis Corneus

Several investigators of the molluscan nervous system have used TEA, injected into presynptic neurones, to determine whether the connexions made by these neurones are monosynaptic. The increase in spike duration produced by the TEA causes an increase in transmitter release, and hence an increase in the amplitude of the postsynaptic potential if the connexion is direct. If the connexion is indirect, the spike in an intercalated neurone will not be affected by the TEA, and the postsynaptic response will remain constant. Experiments described here show that TEA can cross electrotonic junctions in the gastropod mollusc Planorbis corneus. They also show that each TEA-prolonged presynaptic impulse may produce more than one postsynaptic impulse. A larger postsynaptic potential could therefore be produced by presynaptic injection of TEA in the case of an indirect connexion. This indicates that care must be taken when interpreting the results of experiments using TEA to test for monosynaptic connexions.

Synapsin Regulates Basal Synaptic Strength, Synaptic Depression, and Serotonin-Induced Facilitation of Sensorimotor Synapses in Aplysia

2007 ◽  
Vol 98 (6) ◽  
pp. 3568-3580 ◽  
Author(s):  
Diasinou Fioravante ◽  
Rong-Yu Liu ◽  
Anne K. Netek ◽  
Leonard J. Cleary ◽  
John H. Byrne
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Vesicle ◽  
Transmitter Release ◽  
Computational Analysis ◽  
Spontaneous Recovery ◽  
Synaptic Strength ◽  
Short Term ◽  
Homosynaptic Depression ◽  
Heterosynaptic Plasticity

Synapsin is a synaptic vesicle-associated protein implicated in the regulation of vesicle trafficking and transmitter release, but its role in heterosynaptic plasticity remains elusive. Moreover, contradictory results have obscured the contribution of synapsin to homosynaptic plasticity. We previously reported that the neuromodulator serotonin (5-HT) led to the phosphorylation and redistribution of Aplysia synapsin, suggesting that synapsin may be a good candidate for the regulation of vesicle mobilization underlying the short-term synaptic plasticity induced by 5-HT. This study examined the role of synapsin in homosynaptic and heterosynaptic plasticity. Overexpression of synapsin reduced basal transmission and enhanced homosynaptic depression. Although synapsin did not affect spontaneous recovery from depression, it potentiated 5-HT–induced dedepression. Computational analysis showed that the effects of synapsin on plasticity could be adequately simulated by altering the rate of Ca2+-dependent vesicle mobilization, supporting the involvement of synapsin not only in homosynaptic but also in heterosynaptic forms of plasticity by regulating vesicle mobilization.

Characterization of postsynaptic Ca2+ signals at the Drosophila larval NMJ

2011 ◽  
Vol 106 (2) ◽  
pp. 710-721 ◽  
Author(s):  
Sunil A. Desai ◽  
Gregory A. Lnenicka
Keyword(s):  
Transmitter Release ◽  
Postsynaptic Membrane ◽  
Synaptic Activity ◽  
Synaptic Efficacy ◽  
Single Action ◽  
Synaptic Homeostasis ◽  
Multiple Transcripts ◽  
Quantal Size ◽  
Intracellular Ca ◽  
Larval Neuromuscular Junction

Postsynaptic intracellular Ca2+ concentration ([Ca2+]i) has been proposed to play an important role in both synaptic plasticity and synaptic homeostasis. In particular, postsynaptic Ca2+ signals can alter synaptic efficacy by influencing transmitter release, receptor sensitivity, and protein synthesis. We examined the postsynaptic Ca2+ transients at the Drosophila larval neuromuscular junction (NMJ) by injecting the muscle fibers with Ca2+ indicators rhod-2 and Oregon Green BAPTA-1 (OGB-1) and then monitoring their increased fluorescence during synaptic activity. We observed discrete postsynaptic Ca2+ transients along the NMJ during single action potentials (APs) and quantal Ca2+ transients produced by spontaneous transmitter release. Most of the evoked Ca2+ transients resulted from the release of one or two quanta of transmitter and occurred largely at synaptic boutons. The magnitude of the Ca2+ signals was correlated with synaptic efficacy; the Is terminals, which produce larger excitatory postsynaptic potentials (EPSPs) and have a greater quantal size than Ib terminals, produced a larger Ca2+ signal per terminal length and larger quantal Ca2+ signals than the Ib terminals. During a train of APs, the postsynaptic Ca2+ signal increased but remained localized to the postsynaptic membrane. In addition, we showed that the plasma membrane Ca2+-ATPase (PMCA) played a role in extruding Ca2+ from the postsynaptic region of the muscle. Drosophila melanogaster has a single PMCA gene, predicted to give rise to various isoforms by alternative splicing. Using RT-PCR, we detected the expression of multiple transcripts in muscle and nervous tissues; the physiological significance of the same is yet to be determined.

The effect of repetitive stimulation on the passive electrical properties of the presynaptic terminal of the squid giant synapse

1979 ◽  
Vol 206 (1164) ◽  
pp. 293-306 ◽  
Keyword(s):  
Electrical Properties ◽  
Transmitter Release ◽  
Sea Water ◽  
Presynaptic Terminal ◽  
Repetitive Stimulation ◽  
Constant Current ◽  
Current Pulses ◽  
Squid Giant Synapse ◽  
Giant Synapse ◽  
Passive Electrical Properties

The resting electrical properties of the presynaptic terminal of the squid giant synapse have been determined by using constant current pulses. After short periods of repetitive stimulation, the terminal resistance, time constant and capacitance are found to be increased. These changes are absent in terminals bathed in artificial sea water containing no calcium, and sea water containing 5 mM cobalt. It seems likely that these changes are associated with transmitter release.

scholarly journals Kv1.3 channels regulate synaptic transmission in the nucleus of solitary tract

2011 ◽  
Vol 105 (6) ◽  
pp. 2772-2780 ◽  
Author(s):  
Angelina Ramirez-Navarro ◽  
Patricia A. Glazebrook ◽  
Michelle Kane-Sutton ◽  
Caroline Padro ◽  
David D. Kline ◽  
...  
Keyword(s):  
Action Potential ◽  
Transmitter Release ◽  
Brain Slices ◽  
Presynaptic Terminal ◽  
Solitary Tract ◽  
Sensory Afferents ◽  
Peripheral Neurons ◽  
C Fibers ◽  
Nodose Ganglia ◽  
Nucleus Of Solitary Tract

The voltage-gated K+ channel Kv1.3 has been reported to regulate transmitter release in select central and peripheral neurons. In this study, we evaluated its role at the synapse between visceral sensory afferents and secondary neurons in the nucleus of the solitary tract (NTS). We identified mRNA and protein for Kv1.3 in rat nodose ganglia using RT-PCR and Western blot analysis. In immunohistochemical experiments, anti-Kv1.3 immunoreactivity was very strong in internal organelles in the soma of nodose neurons with a weaker distribution near the plasma membrane. Anti-Kv1.3 was also identified in the axonal branches that project centrally, including their presynaptic terminals in the medial and commissural NTS. In current-clamp experiments, margatoxin (MgTx), a high-affinity blocker of Kv1.3, produced an increase in action potential duration in C-type but not A- or Ah-type neurons. To evaluate the role of Kv1.3 at the presynaptic terminal, we examined the effect of MgTx on tract evoked monosynaptic excitatory postsynaptic currents (EPSCs) in brain slices of the NTS. MgTx increased the amplitude of evoked EPSCs in a subset of neurons, with the major increase occurring during the first stimuli in a 20-Hz train. These data, together with the results from somal recordings, support the hypothesis that Kv1.3 regulates the duration of the action potential in the presynaptic terminal of C fibers, limiting transmitter release to the postsynaptic cell.

Clinical-Histopathologic Concordance of Tumors of the Nervous System at the Manuel Velasco Suárez National Institute of Neurology and Neurosurgery in Mexico City

2003 ◽  
Vol 127 (2) ◽  
pp. 187-192
Author(s):  
Leora Velásquez-Pérez ◽  
María Esther Jiménez-Marcial
Keyword(s):  
Nervous System ◽  
A Priori ◽  
World Health ◽  
Cross Sectional ◽  
Diagnostic Uncertainty ◽  
Therapeutic Decisions ◽  
Clinical Diagnoses ◽  
Histopathologic Analysis ◽  
Diagnostic Concordance ◽  
Health Organization

Abstract Context.—When making a diagnosis, the main purpose of clinicians should not be to achieve certainty, but to decrease diagnostic uncertainty in order to make optimal therapeutic decisions. Diagnostic concordance is an essential characteristic if a measurement is to be considered scientific. In the case of tumors of the nervous system (TNS), one of the most accurate diagnostic tests is magnetic resonance imaging. However, histopathologic analyses are essential, because they refine the diagnosis, benefit the patient, and improve our understanding of the disease. By determining the clinical-histopathologic correlation of TNS in one of the main neurologic centers in Mexico, we sought to project reliable morbidity and/or mortality statistics. Objective.—To assess clinical and histopathologic diagnostic agreement in cases involving TNS admitted to the Manuel Velasco Suárez National Institute of Neurology and Neurosurgery between 1990 and 1999. Design.—Cross-sectional diagnostic concordance study, including all clinical hospital records of patients with histopathologically diagnosed TNS, classified according to World Health Organization criteria. Results.—Among 2041 TNS cases, the 3 most frequent types were those affecting the neuroepithelial tissue (32.9%), tumors of the sellar region (29.2%), and tumors of the meninges (25.6%). We found that, overall, clinical-histopathologic concordance for these 3 categories was substantial and statistically significant. Conclusions.—Tumors of the nervous system constitute a heterogeneous group of neoplasms. In the present study, clinical diagnoses substantially agreed with pathologic diagnoses. The a priori clinical diagnosis allowed prompt treatment even before diagnostic confirmation by histopathologic analysis, which is the best way to confirm, clarify, and correct a diagnosis.

Plasticity: Cells, Circuits, Brains, and Behavior

2016 ◽  
Author(s):  
Patricia S. Churchland ◽  
Terrence J. Sejnowski
Keyword(s):  
Nervous System ◽  
Synaptic Plasticity ◽  
Classical Conditioning ◽  
Neuronal Plasticity ◽  
Neural Mechanism ◽  
Synaptic Strength ◽  
Physical Mechanisms ◽  
And Behavior ◽  
The Brain

This chapter examines the physical mechanisms in nervous systems in order to elucidate the structural bases and functional principles of synaptic plasticity. Neuroscientific research on plasticity can be divided into four main streams: the neural mechanism for relatively simple kinds of plasticity, such as classical conditioning or habituation; anatomical and physiological studies of temporal lobe structures, including the hippocampus and the amygdala; study of the development of the visual system; and the relation between the animal's genes and the development of its nervous system. The chapter first considers the role of the mammalian hippocampus in learning and memory before discussing Donald Hebb's views on synaptic plasticity. It then explores the mechanisms underlying neuronal plasticity and those that decrease synaptic strength, the relevance of time with respect to plasticity, and the occurrence of plasticity during the development of the nervous system. It also describes modules, modularity, and networks in the brain.

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