Synaptic plasticity induced by differential manipulation of tonic and phasic motoneurons in Drosophila

Aponte-Santiago, Nicole A.; Ormerod, Kiel G.; Akbergenova, Yulia; Littleton, J Troy

doi:10.1101/2020.04.28.066696

Cited by 7 publications

(9 citation statements)

References 156 publications

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“…Recently, new tools have been developed that enable electrophysiological isolation of MN-Is vs MN-Ib NMJs in Drosophila . In particular, GAL4 driver lines have been identified that enable selective expression in MN-Is or MN-Ib innervating muscle 6 (Aponte-Santiago et al, 2020; Carrillo-Reid et al, 2019; Pérez-Moreno & O’Kane, 2019). In addition, silencing of all neurotransmission from MN-Is or MN-Ib is now possible following the engineering of a botulinum neurotoxin (BoNT-C), which when selectively expressed in MN-Is or MN-Ib silences all neurotransmission without inducing heterosynaptic structural or functional plasticity at the convergent input (Han et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Physiologic and nanoscale distinctions define glutamatergic synapses in tonic vs phasic neurons

Han

et al. 2022

Preprint

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Neurons exhibit a striking degree of functional diversity, each one tuned to the needs of the circuitry in which it is embedded. A fundamental functional dichotomy occurs in activity patterns, with some neurons firing at a relatively constant “tonic” rate, while others fire in bursts - a “phasic” pattern. Synapses formed by tonic vs phasic neurons are also functionally differentiated, yet the bases of their distinctive properties remain enigmatic. A major challenge towards illuminating the synaptic differences between tonic and phasic neurons is the difficulty in isolating their physiological properties. At theDrosophilaneuromuscular junction (NMJ), most muscle fibers are co-innervated by two motor neurons, the tonic “MN-Ib” and phasic “MN-Is”. Here, we employed selective expression of a newly developed botulinum neurotoxin (BoNT-C) transgene to silence tonic or phasic motor neurons. This approach revealed major differences in their neurotransmitter release properties, including probability, short-term plasticity, and vesicle pools. Furthermore, Ca2+imaging demonstrated ~two-fold greater Ca2+influx at phasic neuron release sites relative to tonic, along with enhanced synaptic vesicle coupling. Finally, confocal and super resolution imaging revealed that phasic neuron release sites are organized in a more compact arrangement, with enhanced stoichiometry of voltage-gated Ca2+channels relative to other active zone scaffolds. These data suggest that distinctions in active zone nano-architecture and Ca2+influx collaborate to differentially tune glutamate release at synapses of tonic vs phasic neuronal subtypes.

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Section: Introductionmentioning

confidence: 99%

Physiologic and nanoscale distinctions define glutamatergic synapses in tonic vs phasic neurons

Han

et al. 2022

Preprint

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“…1 A ) (Hoang and Chiba, 2001). Functional differentiation has been demonstrated between terminal types (Kurdyak et al, 1994; Chouhan et al, 2010; Lu et al, 2016; Aponte-Santiago et al, 2020; He et al, 2022; Justs et al, 2022), and between type-Ib terminals on different muscle fibers (Chouhan et al, 2012; Newman et al, 2017; Wang et al, 2021; Justs et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial phosphagen kinases support the volatile power demands of motor nerve terminals

Justs

Sempertegui

Riboul

et al. 2022

Preprint

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Neural function relies on cellular energy supplies meeting the episodic demands of synaptic activity, but little is known about the extent to which power demands (energy demands per unit time) fluctuate, or the mechanisms that match supply with demand. Here, in individually-identified glutamatergic motor neuron terminals of Drosophila larvae, we leveraged prior macroscopic estimates of power demand to generate profiles of power demand from one action potential to the next. These profiles show that signaling demands can exceed non-signaling demands by 17-fold within milliseconds, and terminals with the greatest fluctuation (volatility) in power demand have the greatest mitochondrial volume and packing density. We elaborated on this quantitative approach to simulate adenosine triphosphate (ATP) levels during activity and drove ATP production as a function of the reciprocal of the energy state, but this canonical feedback mechanism appeared to be unable to prevent ATP depletion during locomotion. Muscle cells possess a phosphagen system to buffer ATP levels but phosphagen systems have not been described for motor nerve terminals. We examined these terminals for evidence of a phosphagen system and found the mitochondria to be heavily decorated with an arginine kinase, the key element of invertebrate phosphagen systems. Similarly, an examination of mouse cholinergic motor nerve terminals found mitochondrial creatine kinases, the vertebrate analogues of arginine kinases. Knock down of arginine kinase in Drosophila resulted in rapid depletion of presynaptic ATP during activity, indicating that, in motor nerve terminals, as in muscle, phosphagen systems play a critical role in matching power supply with demand.

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“…Some groups have proposed there exist differences in how the synapse executes PHP at phasic vs. tonic motor terminals (Aponte-Santiago and Littleton, 2020, Genç and Davis, 2019, Newman et al, 2017, Sauvola et al, 2021), depending upon pharamacological vs. genetic challenge. Recent characterization of motor neuron-specific tools allow a refinement of analyses, at least in the context of presynaptic terminals (Han et al, 2022, Aponte-Santiago et al, 2020, Wang et al, 2021). For a second model, a recent study suggests that the type of pharmacological perturbation to glutamate receptors might control the eventual response (Nair et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

The calcineurin regulator Sarah enables distinct forms of homeostatic plasticity at theDrosophilaneuromuscular junction

Armstrong

Frank

2022

Preprint

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The ability of synapses to maintain physiological levels of evoked neurotransmission is essential for neuronal stability. A variety of perturbations can disrupt neurotransmission, but synapses often compensate for disruptions and work to stabilize activity levels, using forms of homeostatic synaptic plasticity. Presynaptic homeostatic potentiation (PHP) is one such mechanism that is expressed at the model Drosophila melanogaster larval neuromuscular junction (NMJ) synapse. In PHP, neurotransmitter release increases in response to challenges to the synapse, resulting in the maintenance of evoked neurotransmission. Prior work separated PHP into two temporal phases, acute and chronic. Those data suggested that cytoplasmic calcium signaling was important for a long-term maintenance of PHP. Here we used a combination of transgenic Drosophila RNA interference and overexpression lines, along with NMJ electrophysiology, synapse imaging, and pharmacology to test if regulators of the calcium/calmodulin-dependent protein phosphatase calcineurin are necessary for the normal expression of acute or chronic forms of PHP. We found that either pre- or postsynaptic dysregulation of a Drosophila gene regulating calcineurin, sarah (sra), blocks PHP. Examination of tissue-specific data showed that increases and decreases in sra expression are both detrimental to PHP. Additionally, the acute and chronic phases of PHP are functionally separable depending entirely upon which sra genetic manipulation is used. Surprisingly, concurrent pre- and postsynaptic sra knockdown or overexpression ameliorated PHP blocks revealed in single tissue experiments. Pharmacological inhibition of calcineurin corroborated this latter finding. Our results suggest that a discrete balance of calcineurin signaling is needed across multiple synapse tissue types and over different temporal phases to stabilize peripheral synaptic outputs.

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Synaptic plasticity induced by differential manipulation of tonic and phasic motoneurons in Drosophila

Cited by 7 publications

References 156 publications

Physiologic and nanoscale distinctions define glutamatergic synapses in tonic vs phasic neurons

Physiologic and nanoscale distinctions define glutamatergic synapses in tonic vs phasic neurons

Mitochondrial phosphagen kinases support the volatile power demands of motor nerve terminals

The calcineurin regulator Sarah enables distinct forms of homeostatic plasticity at theDrosophilaneuromuscular junction

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