Properties of Short-Term Synaptic Depression at Larval Neuromuscular Synapses in Wild-Type and Temperature-Sensitive Paralytic Mutants of Drosophila

2005 ◽  
Vol 93 (5) ◽  
pp. 2396-2405 ◽  
Author(s):  
Ying Wu ◽  
Fumiko Kawasaki ◽  
Richard W. Ordway
Keyword(s):  
Neurotransmitter Release ◽  
Functional Characterization ◽  
Neuromuscular Synapse ◽  
Synaptic Depression ◽  
Temperature Sensitive ◽  
Short Term ◽  
Low Frequencies ◽  
Neuromuscular Synapses ◽  
The Impact

The larval neuromuscular synapse of Drosophila serves as an important model for genetic and molecular analysis of synaptic development and function. Further functional characterization of this synapse, as well as adult neuromuscular synapses, will greatly enhance the impact of this model system on our understanding of synaptic transmission. Here we describe a form of short-term synaptic depression observed at larval, but not adult, neuromuscular synapses and explore the underlying mechanisms. Larval neuromuscular synapses exhibited a form of short-term depression that was strongly dependent on stimulation frequency over a narrow range of low frequencies (0.1–1 Hz). This form of synaptic depression, referred to here as low-frequency short-term depression (LF-STD), results from an activity-dependent reduction in neurotransmitter release. However, in contrast to the predictions of depletion models, the degree of depression was independent of the initial level of neurotransmitter release over a range of extracellular calcium concentrations. This conclusion was confirmed in two temperature-sensitive (TS) paralytic mutants, cacophony and shibire, which exhibit reduced neurotransmitter release resulting from conditional disruption of presynaptic calcium channels and dynamin, respectively. Higher stimulation frequencies (40 or 60 Hz) produced two components of depression that appeared to include LF-STD as well as a more conventional component of short-term depression. These findings reveal novel properties of short-term synaptic depression and suggest that complementary genetic analysis of larval and adult neuromuscular synapses will further define the in vivo mechanisms of neurotransmitter release and short-term synaptic plasticity.

scholarly journals Increased expression of the MALE STERILITY1 transcription factor gene results in temperature-sensitive male sterility in barley

2020 ◽  
Vol 71 (20) ◽  
pp. 6328-6339
Author(s):  
José Fernández-Gómez ◽  
Behzad Talle ◽  
Zoe A Wilson
Keyword(s):  
Transcription Factor ◽  
Male Sterility ◽  
Pollen Development ◽  
Breeding Systems ◽  
Hybrid Breeding ◽  
Temperature Sensitive ◽  
Hybrid Vigour ◽  
Male Sterile ◽  
The Impact

Abstract Understanding the control of fertility is critical for crop yield and breeding; this is particularly important for hybrid breeding to capitalize upon the resultant hybrid vigour. Different hybrid breeding systems have been adopted; however, these are challenging and crop specific. Mutants with environmentally reversible fertility offer valuable opportunities for hybrid breeding. The barley HvMS1 gene encodes a PHD-finger transcription factor that is expressed in the anther tapetum, which is essential for pollen development and causes complete male sterility when overexpressed in barley. This male sterility is due at least in part to indehiscent anthers resulting from incomplete tapetum degeneration, failure of anther opening, and sticky pollen under normal growth conditions (15 °C). However, dehiscence and fertility are restored when plants are grown at temperatures >20 °C, or when transferred to >20 °C during flowering prior to pollen mitosis I, with transfer at later stages unable to rescue fertility in vivo. As far as we are aware, this is the first report of thermosensitive male sterility in barley. This offers opportunities to understand the impact of temperature on pollen development and potential applications for environmentally switchable hybrid breeding systems; it also provides a ‘female’ male-sterile breeding tool that does not need emasculation to facilitate backcrossing.

scholarly journals Synaptic plasticity of inhibitory synapses onto medial olivocochlear efferent neurons

2022 ◽  
Author(s):  
Lester Torres Cadenas ◽  
Hui Cheng ◽  
Catherine J.C. Weisz
Keyword(s):  
Brain Slices ◽  
Synaptic Depression ◽  
Extracellular Calcium ◽  
Outer Hair Cells ◽  
Inhibitory Synapses ◽  
Short Term ◽  
Sound Stimulation ◽  
Efferent Neurons ◽  
Medial Olivocochlear

The descending auditory system modulates the ascending system at every level. The final descending, or efferent stage, is comprised of lateral olivocochlear (LOC) and medial olivocochlear (MOC) neurons. MOC somata in the ventral brainstem project axons to the cochlea to synapse onto outer hair cells (OHC), inhibiting OHC-mediated cochlear amplification. MOC suppression of OHC function is implicated in cochlear gain control with changing sound intensity, detection of salient stimuli, attention, and protection against acoustic trauma. Thus, sound excites MOC neurons to provide negative feedback of the cochlea. Sound also inhibits MOC neurons via medial nucleus of the trapezoid body (MNTB) neurons. However, MNTB-MOC synapses exhibit short-term depression, suggesting reduced MNTB-MOC inhibition during sustained stimuli. Further, due to high rates of both baseline and sound-evoked activity in MNTB neurons in vivo, MNTB-MOC synapses may be tonically depressed. To probe this, we characterized short-term plasticity of MNTB-MOC synapses in mouse brain slices. We mimicked in vivo-like temperature and extracellular calcium conditions, and in vivo-like activity patterns of fast synaptic activation rates, sustained activation, and prior tonic activity. Synaptic depression was sensitive to extracellular calcium concentration and temperature. During rapid MNTB axon stimulation, post-synaptic currents (PSCs) in MOC neurons summated but with concurrent depression, resulting in smaller, sustained currents, suggesting tonic inhibition of MOC neurons during rapid circuit activity. Low levels of baseline MNTB activity did not significantly reduce responses to subsequent rapid activity that mimics sound stimulation, indicating that, in vivo, MNTB inhibition of MOC neurons persists despite tonic synaptic depression.

Short-term culture of ovine embryos modifies fetal myogenesis

1998 ◽  
Vol 274 (6) ◽  
pp. E1121-E1123 ◽  
Author(s):  
E. K. Maxfield ◽  
K. D. Sinclair ◽  
P. J. Broadbent ◽  
T. G. McEvoy ◽  
J. J. Robinson ◽  
...  
Keyword(s):  
Preimplantation Embryos ◽  
Plantaris Muscle ◽  
Short Term ◽  
Fiber Area ◽  
Reproductive Techniques ◽  
Fiber Number ◽  
The Impact ◽  
Short Term Culture

Certain reproductive techniques culture embryos in vitro; however, little is known about the impact of culture on fetal growth. Coculture of day 1ovine zygotes on a bovine granulosa cell layer to blastocysts followed by transfer to synchronous recipients increased fetal weight by 11 and 40% at days 61 and 125, respectively, compared with the transfer of in vivo-produced blastocysts. Plantaris muscle weights were increased by 40% in cultured fetuses at day 125. Examination of myogenesis in plantaris muscle showed that primary fiber number was unchanged at day 61 by culture but that primary fiber area was increased significantly by 15 and 25% at days 61 and 125, respectively; secondary fiber area was increased by 40% at day 125 by culture, and the ratio of secondary to primary fiber numbers was 18–20% greater in the cultured groups compared with the controls at days 61 and 125. The results show that coculture of preimplantation embryos may alter myogenic programming. These changes may contribute to the abnormally large muscles observed in oversize fetuses.

scholarly journals The essential OST2 gene encodes the 16-kD subunit of the yeast oligosaccharyltransferase, a highly conserved protein expressed in diverse eukaryotic organisms.

1995 ◽  
Vol 131 (2) ◽  
pp. 371-383 ◽  
Author(s):  
S Silberstein ◽  
P G Collins ◽  
D J Kelleher ◽  
R Gilmore
Keyword(s):  
Protein Sequence ◽  
Apoptotic Cell ◽  
Functional Characterization ◽  
Glycosylation Site ◽  
Temperature Sensitive ◽  
Microsomal Membranes ◽  
High Mannose ◽  
Eukaryotic Organisms

Oligosaccharyltransferase catalyzes the transfer of a preassembled high mannose oligosaccharide from a dolichol-oligosaccharide donor to consensus glycosylation acceptor sites in newly synthesized proteins in the lumen of the rough endoplasmic reticulum. The Saccharomyces cerevisiae oligosaccharyltransferase is an oligomeric complex composed of six non-identical subunits (alpha-zeta). The alpha, beta, gamma, and delta subunits of the oligosaccharyltransferase are encoded by the OST1, WBP1, OST3, and SWP1 genes, respectively. Here we describe the functional characterization of the OST2 gene that encodes the epsilon-subunit of the oligosaccharyltransferase. Genomic disruption of the OST2 locus was lethal in haploid yeast showing that expression of the Ost2 protein is essential for viability. Overexpression of the Ost2 protein suppresses the temperature-sensitive phenotype of the wbp1-2 allele and increases in vivo and in vitro oligosaccharyltransferase activity in a wbp1-2 strain. An analysis of a series of conditional ost2 mutants demonstrated that defects in the Ost2 protein cause pleiotropic underglycosylation of soluble and membrane-bound glycoproteins. Microsomal membranes isolated from ost2 mutant yeast show marked reductions in the in vitro transfer of high mannose oligosaccharide from exogenous lipid-linked oligosaccharide to a glycosylation site acceptor tripeptide. Surprisingly, the Ost2 protein was found to be 40% identical to the DAD1 protein (defender against apoptotic cell death), a highly conserved protein initially identified in vertebrate organisms. The protein sequence of ost2 mutant alleles revealed mutations at highly conserved residues in the Ost2p/DAD1 protein sequence.

scholarly journals The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e104298 ◽  
Author(s):  
Balázs Szalay ◽  
Áron Cseh ◽  
Gergő Mészáros ◽  
László Kovács ◽  
Attila Balog ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Functional Characterization ◽  
Short Term ◽  
Follow Up Study ◽  
The Impact

scholarly journals Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Diego Zelada ◽  
Francisco J. Barrantes ◽  
Juan Pablo Henríquez
Keyword(s):  
Lithium Chloride ◽  
Nicotinic Acetylcholine Receptors ◽  
Neuromuscular Synapse ◽  
Muscle Fibres ◽  
Similar Response ◽  
Synaptic Organization ◽  
Neuromuscular Synapses ◽  
Postsynaptic Receptors ◽  
The Stability

AbstractLithium chloride has been widely used as a therapeutic mood stabilizer. Although cumulative evidence suggests that lithium plays modulatory effects on postsynaptic receptors, the underlying mechanism by which lithium regulates synaptic transmission has not been fully elucidated. In this work, by using the advantageous neuromuscular synapse, we evaluated the effect of lithium on the stability of postsynaptic nicotinic acetylcholine receptors (nAChRs) in vivo. We found that in normally innervated neuromuscular synapses, lithium chloride significantly decreased the turnover of nAChRs by reducing their internalization. A similar response was observed in CHO-K1/A5 cells expressing the adult muscle-type nAChRs. Strikingly, in denervated neuromuscular synapses, lithium led to enhanced nAChR turnover and density by increasing the incorporation of new nAChRs. Lithium also potentiated the formation of unstable nAChR clusters in non-synaptic regions of denervated muscle fibres. We found that denervation-dependent re-expression of the foetal nAChR γ-subunit was not altered by lithium. However, while denervation inhibits the distribution of β-catenin within endplates, lithium-treated fibres retain β-catenin staining in specific foci of the synaptic region. Collectively, our data reveal that lithium treatment differentially affects the stability of postsynaptic receptors in normal and denervated neuromuscular synapses in vivo, thus providing novel insights into the regulatory effects of lithium on synaptic organization and extending its potential therapeutic use in conditions affecting the peripheral nervous system.

scholarly journals Short-Term Synaptic Depression and Recovery at the Mature Mammalian Endbulb of Held Synapse in Mice

2008 ◽  
Vol 100 (3) ◽  
pp. 1255-1264 ◽  
Author(s):  
Yong Wang ◽  
Paul B. Manis
Keyword(s):  
Synaptic Transmission ◽  
Auditory Nerve ◽  
Synaptic Depression ◽  
Nerve Fibers ◽  
Short Term ◽  
Endbulb Of Held ◽  
Intracellular Ca ◽  
Auditory Nerve Fibers ◽  
Spontaneous Firing Rate

The endbulb of Held synapses between the auditory nerve fibers (ANF) and cochlear nucleus bushy neurons convey fine temporal information embedded in the incoming acoustic signal. The dynamics of synaptic depression and recovery is a key in regulating synaptic transmission at the endbulb synapse. We studied short-term synaptic depression and recovery in mature (P22-38) CBA mice with stimulation rates that were comparable to sound-driven activities recorded in vivo. Synaptic depression in mature mice is less severe (∼40% at 100 Hz) than reported for immature animals and the depression is predominately due to depletion of releasable vesicles. Recovery from depression depends on the rate of activity and accumulation of intracellular Ca2+ at the presynaptic terminal. With a regular stimulus train at 100 Hz in 2 mM external [Ca2+], the recovery from depletion was slow (τslow, ∼2 s). In contrast, a fast (τfast, ∼25 ms), Ca2+-dependent recovery followed by a slower recovery (τslow, ∼2 s) was seen when stimulus rates or external [Ca2+] increased. In normal [Ca2+], recovery from a 100-Hz Poisson-like train is rapid, suggesting that Poisson-like trains produce a higher internal [Ca2+] than regular trains. Moreover, the fast recovery was slowed by approximately twofold in the presence of calmidazolium, a Ca2+/calmodulin inhibitor. Our results suggest that endbulb synapses from high spontaneous firing rate auditory nerve fibers normally operate in a depressed state. The accelerated synaptic recovery during high rates of activity is likely to ensure that reliable synaptic transmission can be achieved at the endbulb synapse.

scholarly journals Altered synaptic plasticity and central pattern generator dysfunction in a Drosophila model of PNKD3 paroxysmal dyskinesia

2020 ◽  
Author(s):  
Simon Lowe ◽  
Patrick Kratschmer ◽  
James E.C. Jepson
Keyword(s):  
Synaptic Plasticity ◽  
Central Pattern Generator ◽  
Neurotransmitter Release ◽  
Ex Vivo ◽  
Pattern Generator ◽  
Bk Channels ◽  
Video Tracking ◽  
Bk Channel ◽  
Short Term

ABSTRACTBackgroundParoxysmal non-kinesigenic dyskinesia type-3 (PNKD3) has been linked to gain-of-function (GOF) mutations in the hSlo1 BK potassium channel, in particular a dominant mutation (D434G) that enhances Ca2+-sensitivity. However, while BK channels play well-known roles in regulating neurotransmitter release, it is unclear whether the D434G mutation alters neurotransmission and synaptic plasticity in vivo. Furthermore, the subtypes of movement-regulating circuits impacted by this mutation are unknown.ObjectivesWe aimed to use a larval Drosophila model of PNKD3 (sloE366G/+) to examine how BK channel GOF in dyskinesia alters synaptic properties and motor circuit function.MethodsWe used video-tracking to test for movement defects in sloE366G/+ larvae, and sharp-electrode recordings to assess the fidelity of Ca2+-dependent neurotransmitter release and short-term plasticity at the neuromuscular junction. We then combined sharp-electrode recording with ex vivo Ca2+-imaging to investigate the functionality of the central pattern generator (CPG) driving foraging behavior in sloE366G/+ larvae.ResultsWe show that the PNKD3 mutation leads to Ca2+-dependent alterations in synaptic release and paired-pulse facilitation. Furthermore, we identify robust alterations in locomotor behaviors in sloE366G/+ larvae which were mirrored by dysfunction of the upstream, movement-generating CPG in the larval ventral nerve cord.ConclusionOur results demonstrate that a BK channel GOF mutation can alter neurotransmitter release and short-term synaptic plasticity, and result in CPG dysfunction, in Drosophila larvae. These data add to a growing body of work linking paroxysmal dyskinesias to aberrant neuronal excitability and synaptic plasticity in pre-motor circuits.

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