Homeostatic control of <i>Drosophila</i> neuromuscular junction function

Frank, C. Andrew; James, Thomas D.; Müller, Martin

doi:10.1002/syn.22133

Cited by 64 publications

(65 citation statements)

References 94 publications

(246 reference statements)

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“…This phenomenon has been described in a variety of systems, including the mammalian central nervous system and the Drosophila neuromuscular junction (NMJ). The HSP at the Drosophila NMJ appears mechanistically distinct from HSP in the mammalian CNS, and therefore will not be covered here (for reviews of this topic see Davis and Müller, 2015;Frank et al, 2020). It should be noted, however, that both innate immune molecules and glia have recently been implicated in HSP at the Drosophila NMJ (Harris et al, 2015;Wang et al, 2020).…”

Section: Homeostatic Synaptic Plasticity (Hsp)mentioning

confidence: 99%

TNF-Mediated Homeostatic Synaptic Plasticity: From in vitro to in vivo Models

Heir

Stellwagen

2020

Front. Cell. Neurosci.

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Since it was first described almost 30 years ago, homeostatic synaptic plasticity (HSP) has been hypothesized to play a key role in maintaining neuronal circuit function in both developing and adult animals. While well characterized in vitro, determining the in vivo roles of this form of plasticity remains challenging. Since the discovery that the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) mediates some forms of HSP, it has been possible to probe some of the in vivo contribution of TNF-mediated HSP. Work from our lab and others has found roles for TNF-HSP in a variety of functions, including the developmental plasticity of sensory systems, models of drug addiction, and the response to psychiatric drugs.

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Section: Homeostatic Synaptic Plasticity (Hsp)mentioning

confidence: 99%

TNF-Mediated Homeostatic Synaptic Plasticity: From in vitro to in vivo Models

Heir

Stellwagen

2020

Front. Cell. Neurosci.

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“…PHP is a well-studied form of homeostatic plasticity at the Drosophila NMJ. Here, rapid pharmacological or chronic genetic manipulations that diminish postsynaptic GluR functionality trigger a trans-synaptic retrograde signaling system that homeostatically increases presynaptic glutamate release to maintain stable synaptic strength (Frank et al, 2020 ). Recently, it was demonstrated that GluR knockdown specifically on muscle 6 can trigger PHP selectively at the subset of synapses innervating muscle 6 without influencing transmission at the synaptic terminals of the same motor neuron that innervate the adjacent muscle 7 (Li et al, 2018a ), demonstrating a remarkable degree of compartmentalized expression of PHP.…”

Section: Resultsmentioning

confidence: 99%

Distinct Target-Specific Mechanisms Homeostatically Stabilize Transmission at Pre- and Post-synaptic Compartments

Goel

Nishimura

Chetlapalli

et al. 2020

Front. Cell. Neurosci.

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Neurons must establish and stabilize connections made with diverse targets, each with distinct demands and functional characteristics. At Drosophila neuromuscular junctions (NMJs), synaptic strength remains stable in a manipulation that simultaneously induces hypo-innervation on one target and hyper-innervation on the other. However, the expression mechanisms that achieve this exquisite target-specific homeostatic control remain enigmatic. Here, we identify the distinct target-specific homeostatic expression mechanisms. On the hypo-innervated target, an increase in postsynaptic glutamate receptor (GluR) abundance is sufficient to compensate for reduced innervation, without any apparent presynaptic adaptations. In contrast, a target-specific reduction in presynaptic neurotransmitter release probability is reflected by a decrease in active zone components restricted to terminals of hyper-innervated targets. Finally, loss of postsynaptic GluRs on one target induces a compartmentalized, homeostatic enhancement of presynaptic neurotransmitter release called presynaptic homeostatic potentiation (PHP) that can be precisely balanced with the adaptations required for both hypo- and hyper-innervation to maintain stable synaptic strength. Thus, distinct anterograde and retrograde signaling systems operate at pre- and post-synaptic compartments to enable target-specific, homeostatic control of neurotransmission.

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“…Presynaptic homeostatic potentiation (PHP) is a well-studied form of homeostatic plasticity at the Drosophila NMJ. Here, rapid pharmacological or chronic genetic manipulations that diminish postsynaptic GluR functionality trigger a trans-synaptic retrograde signaling system that homeostatically increases presynaptic glutamate release to maintain stable synaptic strength (Frank et al, 2020). Recently, it was demonstrated that GluR knockdown specifically on muscle 6 can trigger PHP selectively at the subset of synapses innervating muscle 6 without influencing transmission at the synaptic terminals of the same motor neuron that innervate the adjacent muscle 7 (Li et al, 2018a), demonstrating a remarkable degree of compartmentalized expression of PHP.…”

Section: Resultsmentioning

confidence: 99%

“…Recent studies have shed light on how neurotransmission is stabilized when synaptic growth and function is challenged (Davis and Muller, 2015; Frank et al, 2020; Goel et al, 2019a; Goel et al, 2019b; Li et al, 2018b). However, less is known about how this stability is maintained when neuronal terminals confront diverse and even opposing challenges in synaptic growth and function.…”

Section: Discussionmentioning

confidence: 99%

Distinct target-specific mechanisms homeostatically stabilize transmission at pre-and post-synaptic compartments

Goel

Nishimura²,

Chetlapalli³

et al. 2020

Preprint

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27Neurons must establish and stabilize connections made with diverse targets, each with distinct 28 demands and functional characteristics. At Drosophila neuromuscular junctions, synaptic 29 strength remains stable in a manipulation that simultaneously induces hypo-innervation on one 30 target and hyper-innervation on the other. However, the expression mechanisms that achieve 31 this exquisite target-specific homeostatic control remain enigmatic. Here, we identify the distinct 32 target-specific homeostatic expression mechanisms. On the hypo-innervated target, an increase 33 in postsynaptic glutamate receptor (GluR) abundance is sufficient to compensate for reduced 34 innervation, without any apparent presynaptic adaptations. In contrast, a target-specific 35 reduction in presynaptic neurotransmitter release probability is reflected by a decrease in active 36 zone components restricted to terminals of hyper-innervated targets. Finally, loss of 37 postsynaptic GluRs on one target induces a compartmentalized, homeostatic enhancement of 38 presynaptic neurotransmitter release called presynaptic homeostatic potentiation that can be 39 precisely balanced with the adaptations required for both hypo-and hyper-innervation to 40 maintain stable synaptic strength. Thus, distinct anterograde and retrograde signaling systems 41 operate at pre-and post-synaptic compartments to enable target-specific, homeostatic control of 42 neurotransmission. 43 44 45 46 47 48 49 50 51 52 3 INTRODUCTION 53Synapses are spectacularly diverse in their morphology, physiology, and functional 54 characteristics. These differences are reflected in the molecular composition and abundance of 55 synaptic components at heterogenous synaptic subtypes in central and peripheral nervous 56 systems (Atwood and Karunanithi, 2002; Branco and Staras, 2009; O'Rourke et al., 2012). 57Interestingly, the structure and function of synapses can also vary substantially across terminals 58 of an individual neuron (Fekete et al., 2019; Grillo et al., 2018; Guerrero et al., 2005) and drive 59 input-specific presynaptic plasticity (Letellier et al., 2019). Both Hebbian and homeostatic 60 plasticity mechanisms can work locally and globally at specific synapses to tune synapse 61 function, enabling stable yet flexible ranges of synaptic strength (Diering and Huganir, 2018; 62 Turrigiano, 2012; Vitureira and Goda, 2013). For example, homeostatic receptor scaling globally 63 adjusts GluR abundance, subtype, and/or functionality at dendrites (Turrigiano and Nelson, 642004) yet there is also evidence for synapse specificity (Béïque et al., 2011; Hou et al., 2008; 65 Sutton et al., 2006). Although a number of studies have begun to elucidate the factors that 66 enable both local and global modes of synaptic plasticity at synaptic compartments, it is less 67 appreciated how and why specific synapses undergo plasticity within the context and needs of 68 information transfer in a neural circuit. 69One major force that sculpts the heterogeneity of synaptic strength is impose...

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Homeostatic control of Drosophila neuromuscular junction function

Cited by 64 publications

References 94 publications

TNF-Mediated Homeostatic Synaptic Plasticity: From in vitro to in vivo Models

TNF-Mediated Homeostatic Synaptic Plasticity: From in vitro to in vivo Models

Distinct Target-Specific Mechanisms Homeostatically Stabilize Transmission at Pre- and Post-synaptic Compartments

Distinct target-specific mechanisms homeostatically stabilize transmission at pre-and post-synaptic compartments

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