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 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 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 Glia-neuron signaling mediated by two different BMP ligands impacts synaptic growth

2021 ◽  
Author(s):  
Mathieu Bartoletti ◽  
Tracy Knight ◽  
Aaron Held ◽  
Laura M. Rand ◽  
Kristi A. Wharton
Keyword(s):  
Nervous System ◽  
Neuromuscular Junction ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Neural Development ◽  
Growth Function ◽  
Bmp Signaling ◽  
Autocrine Signaling ◽  
Loss Of Function ◽  
Synaptic Growth

ABSTRACTThe nervous system is a complex network of cells whose interactions provide circuitry necessary for an organism to perceive and move through its environment. Revealing the molecular basis of how neurons and non-neuronal glia communicate is essential for understanding neural development, behavior, and abnormalities of the nervous system. BMP signaling in motor neurons, activated in part by retrograde signals from muscle expressed Gbb (BMP5/6/7) has been implicated in synaptic growth, function and plasticity inDrosophila melanogaster. Through loss-of-function studies, we establish Gbb as a critical mediator of glia to neuron signaling important for proper synaptic growth. Furthermore, the BMP2/4 ortholog, Dpp, expressed in a subset of motor neurons, acts by autocrine signaling to also facilitate neuromuscular junction (NMJ) growth at specific muscle innervation sites. In addition to signaling from glia to motor neurons, autocrine Gbb induces signaling in larval VNC glia which strongly express the BMP type II receptor, Wit. In addition to Dpp’s autocrine motor neuron signaling, Dpp also engages in paracrine signaling to adjacent glia but not to neighboring motor neurons. In one type of dorsal midline motor neuron, RP2,dpptranscription is under tight regulation, as its expression is under autoregulatory control in RP2 but not aCC neurons. Taken together our findings indicate that bi-directional BMP signaling, mediated by two different ligands, facilitates communication between glia and neurons. Gbb, prominently expressed in glia, and Dpp acting from a discrete set of neurons induce active Smad-dependent BMP signaling to influence bouton number during neuromuscular junction growth.

Advances in understanding neuron–glia interactions

2005 ◽  
Vol 2 (1) ◽  
pp. 23-26 ◽  
Author(s):  
R. DOUGLAS FIELDS
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Neuromuscular Junction ◽  
International Symposium ◽  
Synaptic Strength ◽  
System Response ◽  
Myelin Formation ◽  
Recent Advances ◽  
The University

Recent advances in the field of neuron–glia interactions were presented at the 27th International Symposium of the University of Montreal Center de Recherche en Sciences Neruologiques. Topics included synaptogenesis, regulation of synaptic strength by glia at the neuromuscular junction and hippocampus; myelin formation, structure, and maintenance; involvement of glia in nervous-system response to injury, hypoxia, and ischemia; neurogenesis and apoptosis, and microglial involvement in chronic pain.

scholarly journals The Vesicular Acetylcholine Transporter Is Required for Neuromuscular Development and Function

2009 ◽  
Vol 29 (19) ◽  
pp. 5238-5250 ◽  
Author(s):  
Braulio M. de Castro ◽  
Xavier De Jaeger ◽  
Cristina Martins-Silva ◽  
Ricardo D. F. Lima ◽  
Ernani Amaral ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Motor Neurons ◽  
Choline Acetyltransferase ◽  
Knockout Mice ◽  
Synaptic Vesicles ◽  
Electrophysiological Recordings ◽  
Physiological Relevance ◽  
And Function ◽  
Neuromuscular Development ◽  
High Affinity Choline Transporter

ABSTRACT The vesicular acetylcholine (ACh) transporter (VAChT) mediates ACh storage by synaptic vesicles. However, the VAChT-independent release of ACh is believed to be important during development. Here we generated VAChT knockout mice and tested the physiological relevance of the VAChT-independent release of ACh. Homozygous VAChT knockout mice died shortly after birth, indicating that VAChT-mediated storage of ACh is essential for life. Indeed, synaptosomes obtained from brains of homozygous knockouts were incapable of releasing ACh in response to depolarization. Surprisingly, electrophysiological recordings at the skeletal-neuromuscular junction show that VAChT knockout mice present spontaneous miniature end-plate potentials with reduced amplitude and frequency, which are likely the result of a passive transport of ACh into synaptic vesicles. Interestingly, VAChT knockouts exhibit substantial increases in amounts of choline acetyltransferase, high-affinity choline transporter, and ACh. However, the development of the neuromuscular junction in these mice is severely affected. Mutant VAChT mice show increases in motoneuron and nerve terminal numbers. End plates are large, nerves exhibit abnormal sprouting, and muscle is necrotic. The abnormalities are similar to those of mice that cannot synthesize ACh due to a lack of choline acetyltransferase. Our results indicate that VAChT is essential to the normal development of motor neurons and the release of ACh.

Plant hormones, plant growth regulators

2014 ◽  
Vol 155 (26) ◽  
pp. 1011-1018 ◽  
Author(s):  
György Végvári ◽  
Edina Vidéki
Keyword(s):  
Nervous System ◽  
Growth And Development ◽  
Large Scale ◽  
Essential Role ◽  
Higher Plants ◽  
Structure And Function ◽  
Wide Sense ◽  
Large Scale Integration ◽  
Scale Integration ◽  
And Function

Plants seem to be rather defenceless, they are unable to do motion, have no nervous system or immune system unlike animals. Besides this, plants do have hormones, though these substances are produced not in glands. In view of their complexity they lagged behind animals, however, plant organisms show large scale integration in their structure and function. In higher plants, such as in animals, the intercellular communication is fulfilled through chemical messengers. These specific compounds in plants are called phytohormones, or in a wide sense, bioregulators. Even a small quantity of these endogenous organic compounds are able to regulate the operation, growth and development of higher plants, and keep the connection between cells, tissues and synergy beween organs. Since they do not have nervous and immume systems, phytohormones play essential role in plants’ life. Orv. Hetil., 2014, 155(26), 1011–1018.

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