scholarly journals Presynaptic depression maintains stable synaptic strength in developmentally arrested Drosophila larvae

2019 ◽  
Author(s):  
Sarah Perry ◽  
Pragya Goel ◽  
Daniel Miller ◽  
Barry Ganetzky ◽  
Dion Dickman
Keyword(s):  
Neuromuscular Junction ◽  
Time Scales ◽  
Life Stage ◽  
Synaptic Strength ◽  
Muscle Size ◽  
Synaptic Growth ◽  
Long Time ◽  
Presynaptic Release ◽  
And Function ◽  
Synaptic Structures

ABSTRACTPositive and negative modes of regulation typically constrain synaptic growth and function within narrow physiological ranges. However, it is unclear how synaptic strength is maintained when both pre- and post-synaptic compartments continue to grow beyond stages imposed by typical developmental programs. To address whether and how synapses can adjust to a novel life stage for which they were never molded by evolution, we have characterized synaptic growth, structure and function at the Drosophila neuromuscular junction (NMJ) under conditions where larvae are terminally arrested at the third instar stage. While wild type larvae transition to pupae after 5 days, arrested third instar (ATI) larvae persist for up to 35 days, during which NMJs exhibit extensive overgrowth in muscle size, presynaptic release sites, and postsynaptic glutamate receptors. Remarkably, despite this exuberant growth of both pre- and post-synaptic structures, stable neurotransmission is maintained throughout the ATI lifespan through a potent homeostatic reduction in presynaptic neurotransmitter release. Arrest of the larval stage in stathmin mutants reveals a degree of progressive instability and neurodegeneration that was not apparent during the typical larval period. Hence, during a period of unconstrained synaptic growth through an extended developmental period, a robust and adaptive form of presynaptic homeostatic depression can stabilize neurotransmission. More generally, the ATI manipulation provides an attractive system for studying neurodegeneration and plasticity across longer time scales.SIGNIFICANCE STATEMENTIt is unclear whether and how synapses adjust to a novel life stage for which they were never molded by evolution. We have characterized synaptic plasticity at the Drosophila neuromuscular junction in third instar larvae arrested in development for over 35 days. This approach has revealed that homeostatic depression stabilizes synaptic strength throughout the life of arrested third instars to compensate for excessive pre- and post-synaptic growth. This system also now opens the way for the study of synapses and degeneration over long time scales in this powerful model synapse.

scholarly journals A screen for genes that regulate synaptic growth reveals mechanisms that stabilize synaptic strength

2018 ◽  
Author(s):  
Pragya Goel ◽  
Mehak Khan ◽  
Samantha Howard ◽  
Beril Kiragasi ◽  
Koto Kikuma ◽  
...  
Keyword(s):  
Nervous System ◽  
Neuromuscular Junction ◽  
Information Transfer ◽  
Fragile X ◽  
Synaptic Strength ◽  
Zone Structure ◽  
Synaptic Growth ◽  
New Genes ◽  
Electrophysiological Recordings ◽  
And Function

ABSTRACTSynapses grow, prune, and remodel throughout development, experience, and disease. This structural plasticity can destabilize information transfer in the nervous system. However, neural activity remains remarkably stable throughout life, implying that adaptive countermeasures exist to stabilize neurotransmission. Aberrant synaptic structure and function has been associated with a variety of neural diseases including Fragile X syndrome, autism, and intellectual disability. We have screened disruptions in over 300 genes in Drosophila for defects in synaptic growth at the neuromuscular junction. This effort identified 12 mutants with severe reductions or enhancements in synaptic growth. Remarkably, electrophysiological recordings revealed synaptic strength in all but one of these mutants was unchanged compared to wild type. We utilized a combination of genetic, anatomical, and electrophysiological analyses to illuminate three mechanisms that stabilize synaptic strength in the face of alterations in synaptic growth. These include compensatory changes in 1) postsynaptic receptor abundance; 2) presynaptic morphology; and 3) active zone structure. Together, this analysis identifies new genes that regulate synaptic growth and the adaptive strategies that synapses employ to homeostatically stabilize synaptic strength in response.AUTHOR SUMMARYThroughout development, maturation, experience, and disease, synapses undergo dramatic changes in growth and remodeling. Although these processes are necessary for learning and memory, they pose major challenges to stable function in the nervous system. However, neurotransmission is typically constrained within narrow physiological ranges, implying the existence of homeostatic mechanisms that maintain stable functionality despite drastic alterations in synapse number. In this study we investigate the relationship between synaptic growth and function across a variety of mutations in neural and synaptic genes in the fruitfly Drosophila melanogaster. Using the neuromuscular junction as a model system, we reveal three adaptive mechanisms that stabilize synaptic strength when synapses are dramatically under- or over-grown. Together, these findings provide insights into the strategies employed at both pre- and post-synaptic compartments to ensure stable functionality while allowing considerable flexibility in overall synapse number.

scholarly journals Intrinsic Neuronal Determinants Locally Regulate Extrasynaptic and Synaptic Growth at the Adult Neuromuscular Junction

1997 ◽  
Vol 136 (3) ◽  
pp. 679-692 ◽  
Author(s):  
Pico Caroni ◽  
Ludwig Aigner ◽  
Corinna Schneider
Keyword(s):  
Nervous System ◽  
Neuromuscular Junction ◽  
Transgenic Mice ◽  
Structural Changes ◽  
Neuromuscular Junctions ◽  
Structural Plasticity ◽  
Synaptic Growth ◽  
Nerve Sprouting ◽  
Nervous System Function ◽  
Synaptic Structures

Long-term functional plasticity in the nervous system can involve structural changes in terminal arborization and synaptic connections. To determine whether the differential expression of intrinsic neuronal determinants affects structural plasticity, we produced and analyzed transgenic mice overexpressing the cytosolic proteins cortical cytoskeleton–associated protein 23 (CAP-23) and growth-associated protein 43 (GAP-43) in adult neurons. Like GAP-43, CAP-23 was downregulated in mouse motor nerves and neuromuscular junctions during the second postnatal week and reexpressed during regeneration. In transgenic mice, the expression of either protein in adult motoneurons induced spontaneous and greatly potentiated stimulus-induced nerve sprouting at the neuromuscular junction. This sprouting had transgene-specific features, with CAP-23 inducing longer, but less numerous sprouts than GAP-43. Crossing of the transgenic mice led to dramatic potentiation of the sprout-inducing activities of GAP-43 and CAP-23, indicating that these related proteins have complementary and synergistic activities. In addition to ultraterminal sprouting, substantial growth of synaptic structures was induced. Experiments with pre- and postsynaptic toxins revealed that in the presence of GAP-43 or CAP-23, sprouting was stimulated by a mechanism that responds to reduced transmitter release and may be independent of postsynaptic activation. These results demonstrate the importance of intrinsic determinants in structural plasticity and provide an experimental approach to study its role in nervous system function.

scholarly journals Plum is a novel regulator of synaptic function and muscle size in D. melanogaster

2018 ◽  
Author(s):  
Hrvoje Augustin ◽  
Jereme G. Spiers ◽  
Nathaniel S. Woodling ◽  
Joern R. Steinert ◽  
Linda Partridge
Keyword(s):  
Body Weight ◽  
Neuromuscular Junction ◽  
Synaptic Function ◽  
Negative Regulator ◽  
Therapeutic Interventions ◽  
Muscle Size ◽  
Model Organisms ◽  
Neuromuscular System ◽  
Age Related ◽  
And Function

ABSTRACTAlterations in the neuromuscular system underlie several neuromuscular diseases and play critical roles in the development of sarcopenia, the age-related loss of muscle mass and function. Mammalian Myostatin (MST) and GDF11, members of the TGF-β superfamily of growth factors, are powerful regulators of muscle size in both model organisms and humans. Myoglianin (MYO), the Drosophila homolog of MST and GDF11, is a strong inhibitor of synaptic function and structure at the neuromuscular junction (NMJ), and a negative regulator of body weight and muscle size and function in flies. Here, we identified Plum, a cell surface immunoglobulin homologous to mammalian developmental regulators Protogenin and Nope, as a modulator of MYO function in the larval neuromuscular system. Reduction of Plum specifically in the larval body-wall muscles abolishes the previously demonstrated positive effect of attenuated MYO signalling on both muscle size and neuromuscular junction structure and function, likely by de-sequestrating the remaining MYO. In addition, downregulation of Plum on its own results in decreased synaptic strength and body weight, classifying Plum as a (novel) regulator of neuromuscular function and body (muscle) size. These findings offer new insights into possible regulatory mechanisms behind ageing- and disease-related neuromuscular dysfunctions in humans and identify potential targets for therapeutic interventions.

The Spread of Pollutants from Harbour Sludge Depots

1984 ◽  
Vol 16 (3-4) ◽  
pp. 623-633
Author(s):  
M Loxham ◽  
F Weststrate
Keyword(s):  
Time Scales ◽  
Molecular Diffusion ◽  
Near Field ◽  
Parameter Analysis ◽  
Migration Patterns ◽  
Long Time ◽  
Dilution Effects ◽  
Short Time ◽  
Harbour Sludge

It is generally agreed that both the landfill option, or the civil techniques option for the final disposal of contaminated harbour sludge involves the isolation of the sludge from the environment. For short time scales, engineered barriers such as a bentonite screen, plastic sheets, pumping strategies etc. can be used. However for long time scales the effectiveness of such measures cannot be counted upon. It is thus necessary to be able to predict the long term environmenttal spread of contaminants from a mature landfill. A model is presented that considers diffusion and adsorption in the landfill site and convection and adsorption in the underlaying aquifer. From a parameter analysis starting form practical values it is shown that the adsorption behaviour and the molecular diffusion coefficient of the sludge, are the key parameters involved in the near field. The dilution effects of the far field migration patterns are also illustrated.

scholarly journals Mapping of the contraction-induced phosphoproteome identifies TRIM28 as a significant regulator of skeletal muscle size and function

Cell Reports ◽  
2021 ◽  
Vol 34 (9) ◽  
pp. 108796
Author(s):  
Nathaniel D. Steinert ◽  
Gregory K. Potts ◽  
Gary M. Wilson ◽  
Amelia M. Klamen ◽  
Kuan-Hung Lin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Size ◽  
And Function

scholarly journals Orbicularis Oculi Muscle Size and Function: Exploring the Influence of Aging and Exercise Training

Cosmetics ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 29
Author(s):  
Takashi Abe ◽  
Jeremy P. Loenneke
Keyword(s):  
Older Adults ◽  
Exercise Training ◽  
Muscle Hypertrophy ◽  
Peak Velocity ◽  
Muscle Thickness ◽  
Muscle Size ◽  
Sphincter Muscle ◽  
Orbicularis Oculi Muscle ◽  
Orbicularis Oculi ◽  
And Function

The orbicularis oculi muscle is the sphincter muscle of the eyelids that blinks and closes the eyes. In this review, our aim was threefold: (1) to introduce the performance characteristics of blinking activity in young and older adults, (2) to discuss the influence of aging on the orbicularis oculi muscle in healthy adults, and (3) to provide information about the effect of facial exercise training on the orbicularis oculi muscle. To achieve the purpose of this review, a search using two electronic databases (PubMed and Scopus) and a search engine (Google Scholar) was conducted. The amplitude and peak velocity of spontaneously blinking behavior, which is an index of muscle function of the orbicularis oculi, appear to be affected by aging. The muscle thickness of the orbicularis oculi tends to be low in older adults, but there are issues that need to be examined further, such as differences in sex and measurement positions. There was no study on the effect of exercise training; however, the results of a highly trained man indicate that the orbicularis oculi muscles might elicit muscle hypertrophy through non-traditional resistance exercise.

scholarly journals Hydrological response to different time scales of climatological drought: an evaluation of the Standardized Precipitation Index in a mountainous Mediterranean basin

2005 ◽  
Vol 9 (5) ◽  
pp. 523-533 ◽  
Author(s):  
S. M. Vicente-Serrano ◽  
J. I. López-Moreno
Keyword(s):  
Time Scales ◽  
Hydrological Cycle ◽  
Standardized Precipitation Index ◽  
Precipitation Index ◽  
Drought Indices ◽  
Long Time ◽  
The Standardized Precipitation Index ◽  
Hydrological Droughts ◽  
Different Time Scales

Abstract. At present, the Standardized Precipitation Index (SPI) is the most widely used drought index to provide good estimations about the intensity, magnitude and spatial extent of droughts. The main advantage of the SPI in comparison with other indices is the fact that the SPI enables both determination of drought conditions at different time scales and monitoring of different drought types. It is widely accepted that SPI time scales affect different sub-systems in the hydrological cycle due to the fact that the response of the different water usable sources to precipitation shortages can be very different. The long time scales of SPI are related to hydrological droughts (river flows and reservoir storages). Nevertheless, few analyses empirically verify these statements or the usefulness of the SPI time scales to monitor drought. In this paper, the SPI at different time scales is compared with surface hydrological variables in a big closed basin located in the central Spanish Pyrenees. We provide evidence about the way in which the longer (>12 months) SPI time scales may not be useful for drought quantification in this area. In general, the surface flows respond to short SPI time scales whereas the reservoir storages respond to longer time scales (7–10 months). Nevertheless, important seasonal differences can be identified in the SPI-usable water sources relationships. This suggests that it is necessary to test the drought indices and time scales in relation to their usefulness for monitoring different drought types under different environmental conditions and water demand situations.

scholarly journals Nonlinearities of heart rate variability in animal models of impaired cardiac control: contribution of different time scales

2017 ◽  
Vol 123 (2) ◽  
pp. 344-351 ◽  
Author(s):  
Luiz Eduardo Virgilio Silva ◽  
Renata Maria Lataro ◽  
Jaci Airton Castania ◽  
Carlos Alberto Aguiar Silva ◽  
Helio Cesar Salgado ◽  
...  
Keyword(s):  
Nonlinear Dynamics ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Time Scales ◽  
Multiscale Entropy ◽  
Time Frequency ◽  
Cardiac Control ◽  
Long Time ◽  
Nonlinear Features ◽  
Short Time

Heart rate variability (HRV) has been extensively explored by traditional linear approaches (e.g., spectral analysis); however, several studies have pointed to the presence of nonlinear features in HRV, suggesting that linear tools might fail to account for the complexity of the HRV dynamics. Even though the prevalent notion is that HRV is nonlinear, the actual presence of nonlinear features is rarely verified. In this study, the presence of nonlinear dynamics was checked as a function of time scales in three experimental models of rats with different impairment of the cardiac control: namely, rats with heart failure (HF), spontaneously hypertensive rats (SHRs), and sinoaortic denervated (SAD) rats. Multiscale entropy (MSE) and refined MSE (RMSE) were chosen as the discriminating statistic for the surrogate test utilized to detect nonlinearity. Nonlinear dynamics is less present in HF animals at both short and long time scales compared with controls. A similar finding was found in SHR only at short time scales. SAD increased the presence of nonlinear dynamics exclusively at short time scales. Those findings suggest that a working baroreflex contributes to linearize HRV and to reduce the likelihood to observe nonlinear components of the cardiac control at short time scales. In addition, an increased sympathetic modulation seems to be a source of nonlinear dynamics at long time scales. Testing nonlinear dynamics as a function of the time scales can provide a characterization of the cardiac control complementary to more traditional markers in time, frequency, and information domains. NEW & NOTEWORTHY Although heart rate variability (HRV) dynamics is widely assumed to be nonlinear, nonlinearity tests are rarely used to check this hypothesis. By adopting multiscale entropy (MSE) and refined MSE (RMSE) as the discriminating statistic for the nonlinearity test, we show that nonlinear dynamics varies with time scale and the type of cardiac dysfunction. Moreover, as complexity metrics and nonlinearities provide complementary information, we strongly recommend using the test for nonlinearity as an additional index to characterize HRV.

Sign in / Sign up

Export Citation Format

Share Document