The <i>Drosophila</i> Neuromuscular Junction: A Model System for Studying Synaptic Development and Function

Keshishian, Haig; Broadie, Kendal; Chiba, Akira; Bate, Michael

doi:10.1146/annurev.ne.19.030196.002553

Cited by 313 publications

(225 citation statements)

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“…The Drosophila larval NMJ exhibits dynamic functional plasticity resembling that found in vertebrate central synapses (57). To investigate whether presenilin mutations affect synaptic plasticity, we examined paired pulse facilitation (PPF), a form of short-term plasticity at the NMJ.…”

Section: Resultsmentioning

confidence: 99%

Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons

et al. 2006

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It has been shown that presenilin is involved in maintaining Ca 2؉ homeostasis in neurons, including regulating endoplasmic reticulum (ER) Ca 2؉ storage. From studies of primary cultures and cell lines, however, its role in stress-induced responses is still controversial. In the present study we analyzed the effects of presenilin mutations on membrane currents and synaptic functions in response to stress using an in vivo preparation. We examined voltage-gated K ؉ and Ca 2؉ currents at the Drosophila larval neuromuscular junction (NMJ) with voltage-clamp recordings. Our data showed that both currents were generally unaffected by loss-of-function or Alzheimer's disease (AD) -associated presenilin mutations under normal or stress conditions induced by heat shock (HS) or ER stress. In larvae expressing the mutant presenilins, prolonged Ca 2؉ tail current, reflecting slower deactivation kinetics of Ca 2؉ channels, was observed 1 day after stress treatments were terminated. It was further demonstrated that the L-type Ca 2؉ channel was specifically affected under these conditions. Moreover, synaptic plasticity at the NMJ was reduced in larvae expressing the mutant presenilins. At the behavioral level, memory in adult flies was impaired in the presenilin mutants 1 day after HS. The results show that presenilin function is important during the poststress period and its impairment contributes to memory dysfunction observed during adaptation to normal conditions after stress. Our findings suggest a new stress-related mechanism by which presenilin may be implicated in the neuropathology of

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Section: Resultsmentioning

confidence: 99%

Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons

et al. 2006

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“…This dynamic plasticity underlies the activity-dependent refinement of developing neuronal circuits and is thought to be essential for plasticity in the adult brain as well. Due to its accessibility and stereotypic development, the Drosophila glutamitergic neuromuscular junction has become a widely studied model system for investigating the molecular mechanisms that underlie synaptic growth (30). The NMJ forms during late embryogenesis and requires outgrowth of the motor neuron growth cone from the central nervous system, recognition, and contact with its target muscle fiber, and formation of enlargements of the growth cone or "prevaricosities" upon contact with the target muscle.…”

Section: Discussionmentioning

confidence: 99%

Presynaptic N-type Calcium Channels Regulate Synaptic Growth

Rieckhof

Yoshihara

Guan

et al. 2003

Journal of Biological Chemistry

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Voltage-gated calcium channels couple changes in membrane potential to neuronal functions regulated by calcium, including neurotransmitter release. Here we report that presynaptic N-type calcium channels not only control neurotransmitter release but also regulate synaptic growth at Drosophila neuromuscular junctions. In a screen for behavioral mutants that disrupt synaptic transmission, an allele of the N-type calcium channel locus (Dmca1A) was identified that caused synaptic undergrowth. The underlying molecular defect was identified as a neutralization of a charged residue in the third S4 voltage sensor. RNA interference reduction of N-type calcium channel expression also reduced synaptic growth. Hypomorphic mutations in syntaxin-1A or n-synaptobrevin, which also disrupt neurotransmitter release, did not affect synapse proliferation at the neuromuscular junction, suggesting calcium entry through presynaptic N-type calcium channels, not neurotransmitter release per se, is important for synaptic growth. The reduced synapse proliferation in Dmca1A mutants is not due to increased synapse retraction but instead reflects a role for calcium influx in synaptic growth mechanisms. These results suggest Ntype channels participate in synaptic growth through signaling pathways that are distinct from those that mediate neurotransmitter release. Linking presynaptic voltage-gated calcium entry to downstream calciumsensitive synaptic growth regulators provides an efficient activity-dependent mechanism for modifying synaptic strength.

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“…1A & A1). These axonal tracts included the intersegmental nerve (ISN) that innervates dorsal muscles, the segmental nerve SNa that innervates ventral-lateral muscles, and the SNb that innervates medial-lateral muscles (Keshishian et al, 1996;Fig. 1A1).…”

Section: Flamingo Is Expressed In Axons and At Synapsesmentioning

confidence: 99%

The atypical cadherin flamingo regulates synaptogenesis and helps prevent axonal and synaptic degeneration in Drosophila

Bao

Berlanga

Xue

et al. 2007

Molecular and Cellular Neuroscience

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The formation of synaptic connections with target cells and maintenance of axons are highly regulated and crucial for neuronal function. The atypical cadherin and G-protein-coupled receptor Flamingo and its orthologs in amphibians and mammals have been shown to regulate cell polarity, dendritic and axonal growth, and neural tube closure. However, the role of Flamingo in synapse formation and function and in axonal health remains poorly understood. Here we show that fmi mutations cause a significant increase in the number of ectopic synapses on muscles and result in the formation of novel en passant synapses along axons, and unique presynaptic varicosities, including active zones, within axons. fmi mutations also cause defective synaptic responses in a small subset of muscles, an agedependent loss of muscle innervation and a drastic degeneration of axons in 3 rd instar larvae without an apparent loss of neurons. Neuronal expression of Flamingo rescues all of these synaptic and axonal defects and larval lethality. Based on these observations, we propose that Flamingo is required in neurons for synaptic target selection, synaptogenesis, the survival of axons and synapses, and adult viability. These findings shed new light on a possible role for Flamingo in progressive neurodegenerative diseases.

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The Drosophila Neuromuscular Junction: A Model System for Studying Synaptic Development and Function

Cited by 313 publications

References 0 publications

Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons

Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons

Presynaptic N-type Calcium Channels Regulate Synaptic Growth

The atypical cadherin flamingo regulates synaptogenesis and helps prevent axonal and synaptic degeneration in Drosophila

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