Short-term and Long-term Control of Synaptic Strength by Light Activatable Glutamate Receptors at the Drosophila Neuromuscular Junction
Short-term and Long-term Control of Synaptic Strength by Light Activatable Glutamate Receptors at the Drosophila Neuromuscular Junction

Author: Grant Kauwe

Publisher:

Published: 2010

Total Pages: 182

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Drosophila neuromuscular junctions (NMJs) exhibit structural and physiological homeostasis during larval development in which the number of boutons and the amount of neurotransmitter released increases in coordination with larval muscle size growth. The Bone Morphogenetic Protein (BMP) signaling pathway, including Glass bottom-boat (Gbb), a BMP ligand, and Wishful thinking (Wit), its presynaptic BMP receptor, are important for regulating this homeostatic growth in larvae. Genetic analysis of Gbb suggests it is released as a retrograde signal from the postsynaptic muscle to initiate presynaptic BMP signaling for synaptic growth. However, muscle expression of Gbb fails to rescue synaptic transmission defects in the gbb mutant, which is instead rescued by nervous system expression of Gbb. To resolve this conflicting data and elucidate the role of Gbb at the NMJ, we investigated the expression of Gbb during Drosophila development at the NMJ. We fused EclipiticGFP to Gbb for visualizing its expression pattern at third-instar larval NMJs. Finally, we demonstrate genetic rescue of the gbb mutant with our transgenic line and provide evidence that Gbb released from the muscle may play a role in higher order synapses beyond the NMJ. Development of the larval neuromuscular junction (NMJ) in Drosophila has been well characterized using genetic mutants and advanced imaging methods. However, the time course of activity-dependent changes in synaptic strength at the larval NMJ has not yet been fully investigated. To further understand the time course of synaptic plasticity at the NMJ, we used the Gal4/UAS system to express the Light-Gated Glutamate Receptor (LiGluR) in the muscle to precisely control postsynaptic activity while performing electrophysiological recordings. Our experiments reveal that long-term postsynaptic LiGluR expression during development induces a homeostatic decrease in bouton density and evoked synaptic transmission. With acute activation of LiGluRs, we potentiate synaptic transmission during high frequency stimulation. CamKII activity is required for this enhancement in synaptic strength by rapid LiGluR activation but it is not necessary for the long-term decrease in bouton density. Finally, we provide evidence that suggests the Wit BMP receptor is not required for the rapid potentiation of synaptic transmission but we provide data to possibly implicate cAMP signaling as a downstream mediator of this effect. These results suggest that a transient increase in postsynaptic activity generated by LiGluR activation may produce a rapid retrograde signal that enhances neurotransmitter release.

Kismet-dependent Regulation of Glutamate Receptor Clustering and Synaptic Transmission at the Drosophila Neuromuscular Junction
Kismet-dependent Regulation of Glutamate Receptor Clustering and Synaptic Transmission at the Drosophila Neuromuscular Junction

Author: Rupa Ghosh

Publisher:

Published: 2014

Total Pages: 406

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The Drosophila neuromuscular junction (NMJ) is a glutamatergic synapse that is structurally and functionally similar to mammalian glutamatergic synapses. These synapses can, as a result in changes in activity, alter the strength of their connections via processes that require chromatin remodeling and changes in gene expression. The chromodomain helicase binding domain (CHD) protein Kismet (Kis) is expressed in both the presynaptic motor neuron nuclei and postsynaptic muscle nuclei of the Drosophila NMJ. Here we show that Kis is involved in the localization and clustering of glutamate receptors in postsynaptic muscle cells, in the proper morphology of presynaptic motor neurons, in larval motor behavior, and in synaptic transmission. Our data suggests that Kis is part of the machinery that modulates the development and function of this synapse. Kis is the homolog to human CHD7, which is mutated in CHARGE syndrome. Thus, our data may suggest novel avenues of investigation for synaptic defects associated with CHARGE syndrome.

NMDA Receptor-dependent Long-term Potentiation of Slow Synaptic Inhibition in Hippocampus
NMDA Receptor-dependent Long-term Potentiation of Slow Synaptic Inhibition in Hippocampus

Author: Shen Cindy Huang

Publisher:

Published: 2005

Total Pages: 280

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Synaptic plasticity, the cellular correlate for learning and memory, involves a number of molecules that reside in the dendritic spine. For example, long-term potentiation (LTP) of the excitatory postsynaptic current (EPSC) is induced by postsynaptic NMDA receptor and Ca 2+ /calmodulin-dependent kinase II (CaMKII) activity. Intrigued by recent findings that dendritic spines also harbor the metabotropic GABA B receptor for the major inhibitory transmitter GABA, as well as its downstream effector the G protein-activated inwardly rectifying K + (GIRK) channel, we wondered whether pairing glutamate release with postsynaptic depolarization would affect the slow inhibitory postsynaptic current (sIPSC) mediated by GABA B receptors and GIRK channels. Remarkably, we found that the same signaling pathway for inducing LTP of the EPSC also potentiated the sIPSC. Moreover, in mice lacking Nova-2, which is targeted in paraneoplastic opsoclonus myoclonus ataxia (POMA) patients and binds RNAs for synaptic proteins, the hippocampal CA1 neurons exhibited no LTP of slow synaptic inhibition.

Molecular Mechanisms that Regulate Synaptic Efficacy at the Drosophila Neuromuscular Junction
Molecular Mechanisms that Regulate Synaptic Efficacy at the Drosophila Neuromuscular Junction

Author: Stephanie D. Albin

Publisher:

Published: 2006

Total Pages: 298

ISBN-13:

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The molecular mechanisms underlying the retrograde control of presynaptic neurotransmitter release at the NMJ are not well understood. Here we describe the identification of the first known inhibitor of synaptic homeostasis. Identification of the pathways through which this inhibitor act may eventually lead to a greater understanding of the mechanisms that regulate homeostasis.