Molecular logic of synaptic diversity between Drosophila tonic and phasic motoneurons

Neuron, Год журнала: 2023, Номер 111(22), С. 3554 - 3569.e7

Опубликована: Авг. 22, 2023

Although neuronal subtypes display unique synaptic organization and function, the underlying transcriptional differences that establish these features are poorly understood. To identify molecular pathways contribute to diversity, single-neuron Patch-seq RNA profiling was performed on Drosophila tonic phasic glutamatergic motoneurons. Tonic motoneurons form weaker facilitating synapses onto single muscles, while stronger depressing multiple muscles. Super-resolution microscopy in vivo imaging demonstrated active zones more compact enhanced Ca2+ influx compared with their counterparts. Genetic analysis identified properties mapped gene expression for several cellular pathways, including distinct signaling ligands, post-translational modifications, intracellular buffers. These findings provide insights into how transcriptomes drive functional morphological between subtypes.

Язык: Английский

---

Homeostatic control of Drosophila neuromuscular junction function

Synapse, Год журнала: 2019, Номер 74(1)

Опубликована: Сен. 26, 2019

Abstract The ability to adapt changing internal and external conditions is a key feature of biological systems. Homeostasis refers regulatory process that stabilizes dynamic systems counteract perturbations. In the nervous system, homeostatic mechanisms control neuronal excitability, neurotransmitter release, receptors, neural circuit function. neuromuscular junction (NMJ) Drosophila melanogaster has provided wealth molecular information about how synapses implement forms synaptic plasticity, with focus on transsynaptic, modulation release. This review examines some recent findings from NMJ highlights questions field will ponder in coming years.

Язык: Английский

---

Synaptic Plasticity Induced by Differential Manipulation of Tonic and Phasic Motoneurons in Drosophila

Journal of Neuroscience, Год журнала: 2020, Номер 40(33), С. 6270 - 6288

Опубликована: Июль 6, 2020

Structural and functional plasticity induced by neuronal competition is a common feature of developing nervous systems. However, the rules governing how postsynaptic cells differentiate between presynaptic inputs are unclear. In this study, we characterized synaptic interactions following manipulations tonic Ib or phasic Is glutamatergic motoneurons that coinnervate muscles male female Drosophila melanogaster larvae. After identifying drivers for each subtype, performed ablation genetic to alter activity examined effects on innervation function at neuromuscular junctions. Ablation either resulted in decreased muscle response, with some compensation occurring input when was missing. contrast, terminal failed show structural changes loss coinnervating input. Decreasing neuron tetanus toxin light chain innervation. Decreased reduced active zone (AZ) number subsynaptic reticulum volume, emergence filopodial-like protrusions from boutons did not induce its own synapses, but motoneuron increased AZs it formed. These findings indicate respond independently activity, alterations input, respectively. SIGNIFICANCE STATEMENT Both invertebrate vertebrate systems display response behavioral experiences, indicating underlying mechanisms emerged early evolution. How specific classes innervating same target distinct types Here, whether Drosophila competitive cooperative during muscle, compensatory output one altered. We established system differentially manipulate cell type-specific inputs. Our differently mismatch subclass responding robustly compared motoneurons.

Язык: Английский

---

Active zone compaction correlates with presynaptic homeostatic potentiation

Cell Reports, Год журнала: 2021, Номер 37(1), С. 109770 - 109770

Опубликована: Окт. 1, 2021

Neurotransmitter release is stabilized by homeostatic plasticity. Presynaptic potentiation (PHP) operates on timescales ranging from minute- to life-long adaptations and likely involves reorganization of presynaptic active zones (AZs). At Drosophila melanogaster neuromuscular junctions, earlier work ascribed AZ enlargement incorporating more Bruchpilot (Brp) scaffold protein a role in PHP. We use localization microscopy (direct stochastic optical reconstruction [dSTORM]) hierarchical density-based spatial clustering applications with noise (HDBSCAN) study plasticity during PHP at the synaptic mesoscale. find compaction individual AZs acute philanthotoxin-induced chronic genetically induced but unchanged copy numbers proteins. Compaction even occurs level Brp subclusters, which move toward centers, Rab3 interacting molecule (RIM)-binding (RBP) subclusters. Furthermore, correlative confocal dSTORM imaging reveals how translates into apparent increases area content, as implied earlier.

Язык: Английский

---

Physiologic and Nanoscale Distinctions Define Glutamatergic Synapses in Tonic vs Phasic Neurons

Journal of Neuroscience, Год журнала: 2023, Номер 43(25), С. 4598 - 4611

Опубликована: Май 23, 2023

Neurons exhibit a striking degree of functional diversity, each one tuned to the needs circuitry in which it is embedded. A fundamental dichotomy occurs activity patterns, with some neurons firing at relatively constant "tonic" rate, while others fire bursts, "phasic" pattern. Synapses formed by tonic versus phasic are also functionally differentiated, yet bases their distinctive properties remain enigmatic. major challenge toward illuminating synaptic differences between and difficulty isolating physiological properties. At Drosophila neuromuscular junction, most muscle fibers coinnervated two motor neurons: "MN-Ib" "MN-Is." Here, we used selective expression newly developed botulinum neurotoxin transgene silence or larvae either sex. This approach highlighted neurotransmitter release properties, including probability, short-term plasticity, vesicle pools. Furthermore, Ca2+ imaging demonstrated ∼2-fold greater influx neuron sites relative tonic, along an enhanced coupling. Finally, confocal super-resolution revealed that organized more compact arrangement, stoichiometry voltage-gated channels other active zone scaffolds. These data suggest distinctions nano-architecture collaborate differentially tune glutamate subtypes.SIGNIFICANCE STATEMENT "Tonic" neuronal subtypes, based on differential common across many nervous systems. Using recently selectively transmission from these neurons, reveal specialized structural distinguish neurons. study provides important insights into how input-specific diversity achieved, could have implications for neurologic disorders involve changes function.

Язык: Английский

---

Distinct input-specific mechanisms enable presynaptic homeostatic plasticity

Science Advances, Год журнала: 2025, Номер 11(7)

Опубликована: Фев. 14, 2025

Synapses are endowed with the flexibility to change through experience, but must be sufficiently stable last a lifetime. This tension is illustrated at Drosophila neuromuscular junction (NMJ), where two motor inputs that differ in structural and functional properties coinnervate most muscles coordinate locomotion. To stabilize NMJ activity, neurons augment neurotransmitter release following diminished postsynaptic glutamate receptor functionality, termed presynaptic homeostatic potentiation (PHP). How these distinct contribute PHP plasticity remains enigmatic. We have used botulinum neurotoxin selectively silence each input resolve their roles PHP, demonstrating specific: Chronic (genetic) targets tonic MN-Ib, active zone remodeling enhances Ca 2+ influx promote increased release. In contrast, acute (pharmacological) increases vesicle pools potentiate phasic MN-Is. Thus, modulations nanoarchitecture, pools, collaborate enable input-specific expression.

Язык: Английский

---

Cul3 and insomniac are required for rapid ubiquitination of postsynaptic targets and retrograde homeostatic signaling

Nature Communications, Год журнала: 2019, Номер 10(1)

Опубликована: Июль 5, 2019

At the Drosophila neuromuscular junction, inhibition of postsynaptic glutamate receptors activates retrograde signaling that precisely increases presynaptic neurotransmitter release to restore baseline synaptic strength. However, nature underlying induction process remains enigmatic. Here, we design a forward genetic screen discover factors in compartment necessary generate homeostatic signaling. This approach identified insomniac (inc), putative adaptor for Cullin-3 (Cul3) ubiquitin ligase complex, which together with Cul3 is essential normal sleep regulation. Interestingly, find Inc and rapidly accumulate at compartments following acute receptor are required local increase mono-ubiquitination. Finally, show Peflin, Ca2+-regulated co-adaptor, communication, suggesting relationship between Ca2+ control Cul3/Inc activity compartment. Our study suggests Cul3/Inc-dependent mono-ubiquitination, compartmentalized densities, gates provides an intriguing molecular link plasticity synapses.

Язык: Английский

---

Synapse development and maturation at the drosophila neuromuscular junction

Neural Development, Год журнала: 2020, Номер 15(1)

Опубликована: Авг. 2, 2020

Synapses are the sites of neuron-to-neuron communication and form basis neural circuits that underlie all animal cognition behavior. Chemical synapses specialized asymmetric junctions between a presynaptic neuron postsynaptic target through series diverse cellular subcellular events under control complex signaling networks. Once established, synapse facilitates neurotransmission by mediating organization fusion synaptic vesicles must also retain ability to undergo plastic changes. In recent years, genes have been implicated in wide array neurodevelopmental disorders; individual societal burdens imposed these disorders, as well lack effective therapies, motivates continued work on fundamental biology. The properties functions nervous system remarkably conserved across phyla, many insights into vertebrate central derived from studies invertebrate models. A prominent model is Drosophila melanogaster larval neuromuscular junction, which bears striking similarities glutamatergic brain spine; further advantages include simplicity experimental versatility fly, its century-long history organism. Here, we survey findings major synaptogenesis, including specification, morphogenesis, assembly maturation specializations, with emphasis conducted at junction.

Язык: Английский

---

Synaptic Properties and Plasticity Mechanisms of Invertebrate Tonic and Phasic Neurons

Frontiers in Physiology, Год журнала: 2020, Номер 11

Опубликована: Дек. 16, 2020

Defining neuronal cell types and their associated biophysical synaptic diversity has become an important goal in neuroscience as a mechanism to create comprehensive brain atlases the post-genomic age. Beyond broad classification such neurotransmitter expression, interneuron vs. pyramidal, sensory or motor, field is still early stages of understanding closely related types. In both vertebrate invertebrate nervous systems, one well-described distinction firing characteristics release properties are tonic phasic subtypes. vertebrates, these classes were defined based on sustained responses during stimulation (tonic) transient that rapidly adapt (phasic). crustaceans, expanded include properties, with motoneurons displaying weaker synapses undergo short-term facilitation maintain muscle contraction posture. contrast, stronger showed rapid depression recruited for short bursts fast locomotion. Tonic similarities those crustaceans have been characterized Drosophila, allowing genetic toolkit this model be used dissecting unique plasticity mechanisms This review outlines general highlights recent advances characterize distinct pathways two glutamatergic drive

Язык: Английский

---

Maintenance of homeostatic plasticity at the Drosophila neuromuscular synapse requires continuous IP3-directed signaling

eLife, Год журнала: 2019, Номер 8

Опубликована: Июнь 10, 2019

Synapses and circuits rely on neuroplasticity to adjust output meet physiological needs. Forms of homeostatic synaptic plasticity impart stability at synapses by countering destabilizing perturbations. The Drosophila melanogaster larval neuromuscular junction (NMJ) is a model synapse with robust expression plasticity. At the NMJ, system detects impaired postsynaptic sensitivity neurotransmitter activates retrograde signal that restores function adjusting release. This process has been separated into temporally distinct phases, induction maintenance. One prevailing hypothesis shared mechanism governs both phases. Here, we show two phases are separable. Combining genetics, pharmacology, electrophysiology, find signaling consisting PLCβ, inositol triphosphate (IP3), IP3 receptors, Ryanodine receptors required only for maintenance We also NMJ capable inducing even when its sustained absent. Editorial note: article through an editorial in which authors decide how respond issues raised during peer review. Reviewing Editor's assessment all have addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

Язык: Английский

---