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

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Neuromuscular basis of Drosophila larval rolling escape behavior

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(51)

Опубликована: Дек. 14, 2023

When threatened by dangerous or harmful stimuli, animals engage in diverse forms of rapid escape behaviors. In Drosophila larvae, one type response involves C-shaped bending and lateral rolling followed forward crawling. The sensory circuitry that promotes larval has been extensively characterized; however, the motor programs underlying are unknown. Here, we characterize neuromuscular basis behavior. We used high-speed, volumetric, Swept Confocally Aligned Planar Excitation (SCAPE) microscopy to image muscle activity during rolling. Unlike sequential peristaltic contractions progress from segment backward crawling, progresses circumferentially propose progression muscular contraction around larva's circumference results a transient misalignment between weight ground support forces, which generates torque induces stabilizing body rotation. Therefore, successive cycles slight reactive aligning rotation lead continuous motion. Supporting our biomechanical model, found disrupting groups undergoing circumferential leads defects. use EM connectome data identify premotor connectivity patterns could drive behavior perform neural silencing approaches demonstrate crucial role group glutamatergic neurons Our reveal body-wide putative circuit organization for execution response.

Язык: Английский

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scRNA-seq data from the larval Drosophila ventral cord provides a resource for studying motor systems function and development

Developmental Cell, Год журнала: 2024, Номер 59(9), С. 1210 - 1230.e9

Опубликована: Апрель 2, 2024

Язык: Английский

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Ca2+ channel and active zone protein abundance intersects with input-specific synapse organization to shape functional synaptic diversity

eLife, Год журнала: 2024, Номер 12

Опубликована: Сен. 18, 2024

Synaptic heterogeneity is a hallmark of nervous systems that enables complex and adaptable communication in neural circuits. To understand circuit function, it thus critical to determine the factors contribute functional diversity synapses. We investigated contributions voltage-gated calcium channel (VGCC) abundance, spatial organization, subunit composition synapse among between synapses formed by two closely related Drosophila glutamatergic motor neurons with distinct neurotransmitter release probabilities (P r ). Surprisingly, VGCC levels are highly predictive heterogeneous P individual either low- or high-P inputs, but not inputs. find same number VGCCs more densely organized at synapses, consistent tighter VGCC-synaptic vesicle coupling. generated endogenously tagged lines investigate subunits vivo found α2δ–3 Straightjacket along CAST/ELKS active zone (AZ) protein Bruchpilot, both key regulators VGCCs, less abundant yet positively correlate input. Consistently, Bruchpilot dynamically increased across AZs inputs when potentiated maintain stable following glutamate receptor inhibition. Together, these findings suggest model which AZ abundance intersects input-specific molecular organization shape

Язык: Английский

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Active zone maturation state controls synaptic output and release mode and is differentially regulated by neuronal activity

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

Abstract Synapse formation requires the gradual accumulation of cytomatrix proteins and voltage-gated Ca 2+ channels (VDCCs) at presynaptic active zones (AZs) to support neurotransmitter release. To correlate AZ maturation with synaptic output, quantal imaging was performed serially imaged time-stamped Drosophila synapses. Evoked release strength correlated strongly age late scaffolds, while immature sites lacking VDCC supported spontaneous examine how neuronal activity regulates protein accumulation, effects disruptions SV fusion or action potential generation were analyzed. Decreasing reduced seeding caused hyperaccumulation material existing AZs. Although enlarged AZs are also observed in rab3 mutants, reduction acted through an independent mechanism that required postsynaptic glutamate receptor-dependent signaling. Together, these data indicate state sets distinct modes output strength, shaping both number size across development.

Язык: Английский

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Building and modifying diverse synaptic properties: Insights from Drosophila

Current Opinion in Neurobiology, Год журнала: 2025, Номер 92, С. 102995 - 102995

Опубликована: Март 9, 2025

Язык: Английский

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Synchronization in epithelial tissue morphogenesis

Current Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Balanced synapse-to-synapse short-term plasticity ensures constant transmitter release

Current Biology, Год журнала: 2025, Номер unknown

Опубликована: Июнь 1, 2025

Synaptic strength can vary greatly between synapses. Optical quantal analysis at Drosophila glutamatergic motor neuron synapses shows that short-term plasticity also varies synapses, even those made by an individual neuron. Strong and weak are randomly distributed in the nerve terminal, as facilitating depressing Although exhibit highly heterogeneous basal low-action potential firing frequency undergo varied when increases, overall distribution of across remains remarkably constant due to a balance number facilitate versus depress their degree synaptic weight. Constancy transmitter release ensure robustness changing behavioral conditions.

Язык: Английский

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To Ib or not to b: Transcriptional regulation of tonic type Ib vs. phasic type Is motor neurons

Neuron, Год журнала: 2023, Номер 111(22), С. 3497 - 3499

Опубликована: Ноя. 1, 2023

Язык: Английский

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PTPN11/Corkscrew activates local presynaptic MAPK signaling to regulate Synapsin, synaptic vesicle pools, and neurotransmission strength, with a dual requirement in neurons and glia

Journal of Neuroscience, Год журнала: 2024, Номер unknown, С. e1077232024 - e1077232024

Опубликована: Март 12, 2024

Cytoplasmic protein tyrosine phosphatase (PTP) non-receptor type 11 (PTPN11) and Drosophila homolog Corkscrew (Csw) regulate the mitogen-activated kinase (MAPK) pathway via a conserved autoinhibitory mechanism. Disease causing loss-of-function (LoF) gain-of-function (GoF) mutations both disrupt this autoinhibition to potentiate MAPK signaling. At neuromuscular junction (NMJ) glutamatergic synapse, LoF/GoF elevate transmission strength reduce activity-dependent synaptic depression. In sexes of mutations, vesicles (SV) colocalized Synapsin phosphoprotein tether is highly elevated at rest, but quickly reduced with stimulation, suggesting larger SV reserve pool greatly heightened recruitment. Transmission electron microscopy mutants reveals an number SVs clustered presynaptic active zones, that increased vesicle availability causative for neurotransmission. Direct neuron-targeted extracellular signal-regulated (ERK) GoF phenocopies local MAPK/ERK signaling in mutants, confirming regulatory loss blocks elevation PTPN11 ERK mutants. However, csw null cannot be rescued by wildtype Csw neurons: neurotransmission only expressing neurons glia simultaneously. Nevertheless, targeted either or alone recapitulates Thus, PTPN11/Csw cell sufficient upregulate function, dual requirement necessary Taken together, we conclude acts glia, LoF similarly upregulating enhance Synapsin-mediated trafficking. Significance statement Noonan syndrome (NS) is, far, most common RASopathy; group clinically-classified genetic syndromes caused alterations: it affects 1 every 1000-2000 people. Patients present cognitive deficits mutations; basis NS, resulting NS multiple lentigines (NSML). We find NS/NSML patient-derived as well corkscrew all increase signaling, turnover, release sites. Surprisingly, PTPN11/corkscrew required control strength. These findings suggest disease interventions manipulating trafficking mechanisms, therapeutic strategies targeting neurons.

Язык: Английский

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