Experience-dependent glial pruning of synaptic glomeruli during the critical period

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Апрель 20, 2024

Abstract Critical periods are temporally-restricted, early-life windows when sensory experience remodels synaptic connectivity to optimize environmental input. In the Drosophila juvenile brain, critical period drives synapse elimination, which is transiently reversible. Within olfactory neuron (OSN) classes synapsing onto single projection neurons extending brain learning/memory centers, we find glia mediate experience-dependent pruning of OSN glomeruli downstream odorant exposure. We glial projections infiltrate neuropil in response experience, and use Draper (MEGF10) engulfment receptors prune glomeruli. Downstream, antagonistic Basket (JNK) Puckered (DUSP) signaling required for translocation activated into nuclei. Dependent on this signaling, expression F-actin linking scaffold Cheerio (FLNA), absolutely essential pruning. mediates regulation cytoskeleton remodeling. These results define a sequential pathway strictly-defined period; input infiltration projections, Draper/MEGF10 activate Basket/JNK cascade transcriptional activation, Cheerio/FLNA induction regulates actin targeted phagocytosis.

Язык: Английский

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Balance of activity during a critical period tunes a developing network

eLife, Год журнала: 2024, Номер 12

Опубликована: Янв. 9, 2024

Developing neural circuits are influenced by activity and especially sensitive to changes in during critical periods (CPs) of development. Changes occurring a CP often become ‘locked in’ so that they affect the mature network. Indeed, several neurodevelopmental disorders have been linked excessive such periods. It is, therefore, important identify those aspects circuit development CP. In this study, we take advantage genetic tractability Drosophila show perturbation an embryonic permanently alters properties locomotor circuit. Specific include increased synchronicity motoneuron greater strengthening excitatory over inhibitory synaptic drive motoneurons. These sufficient reduce network robustness, evidenced sensitivity induced seizure. We also can rescue these when is mitigated inhibition provided mechanosensory neurons. Similarly, demonstrate dose-dependent relationship between experienced extent which it possible hyperexcitable phenotype characteristic para bss mutation. This suggests developing must be exposed properly balanced sum excitation achieve normal function. Our results, provide novel insight into how shapes specific elements circuit, period integrated tune environment will likely

Язык: Английский

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Modulation of a critical period for motor development in Drosophila by BK potassium channels

Current Biology, Год журнала: 2024, Номер 34(15), С. 3488 - 3505.e3

Опубликована: Июль 24, 2024

Язык: Английский

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Neuron-to-glia and glia-to-glia signaling directs critical period experience-dependent synapse pruning

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Фев. 18, 2025

Experience-dependent glial synapse pruning plays a pivotal role in sculpting brain circuit connectivity during early-life critical periods of development. Recent advances suggest layered cascade intercellular communication between neurons and phagocytes orchestrates this precise, targeted elimination. We focus here on studies from the powerful Drosophila forward genetic model, with reference to complementary findings mouse work. present both neuron-to-glia glia-to-glia signaling pathways directing experience-dependent pruning. discuss putative hierarchy secreted long-distance cues cell surface short-distance that act sequentially orchestrate glia activation, infiltration, target recognition, engulfment, then phagocytosis for Ligand-receptor partners mediating these stages different contexts are discussed recent studies. Signaling include phospholipids, small neurotransmitters, insulin-like peptides, proteins. Conserved receptors ligands discussed, together mechanisms where receptor identity remains unknown. Potential proposed tight temporal-restriction heightened elimination periods, as well potential means re-open such plasticity at maturity.

Язык: Английский

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Circadian control in the timing of critical periods during Drosophila larval neuronal development

Current Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Developing neural circuits are maximally open to modification during defined critical periods (CPs).1,2,3,4 We previously identified a CP in the Drosophila embryo, from 17 19 h after egg laying (AEL), which activity manipulation (optogenetic and/or pharmacological) permanently alters locomotor network stability.5,6 Analysis of excitatory and inhibitory inputs an motoneuron shows that preferentially enhances excitation.7 This effect is permanent, persisting through third instars (5 days post manipulation). A manifestation this marked increase seizure recovery time (RT) response electric shock. The induced results immediate paralysis, followed by uncoordinated peristalsis until larva recovers sufficiently move away its original position (i.e., endpoint).6 Significantly, exposure blue light (BL) same embryonic temporal window similarly able lead increased RT, requires presence CRYPTOCHROME (CRY).8 Here, we identify series BL-sensitive CPs, occurring at ∼24-h intervals, embryogenesis larval development. Exposure BL these CPs increases taken for wandering larvae recover electroshock-induced activity. absent when CRY or principal clock-signaling neuropeptide-pigment-dispersing factor (PDF)-is absent. Thus, uncover novel role circadian clock stages

Язык: Английский

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Assembly of a functional neuronal circuit in embryos of an ancestral metazoan is influenced by temperature and the microbiome

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(23)

Опубликована: Июнь 5, 2025

Understanding how neural populations emerge to give rise behavior is a major goal in neuroscience. Here, we explore the self-assembly of circuits Hydra , an organism with simple nervous system but no centralized information processing, enhance understanding evolution. We define as spontaneous organization neurons into functional without requiring prespecified structural template. In this context, N4 neuronal circuit, which have previously found be particularly important feeding animal, develops embryos through activity-driven self-assembly, process intrinsic calcium activity drives connectivity and synchronization among spatially distributed over time. Gap junctions vesicle-mediated communication between non-neuronal cells drive rapid assembly, embryo’s prospective oral region exhibiting highest density. An artificial electrical circuit–based model biophysically inspired simulation demonstrates dynamic increases time, along predictions for selective adaptions connections. Environmental factors, like temperature absent microbiome, modify architecture, suggesting existence certain adaptability during development. propose that these fundamental features originated last common bilaterian ancestor, supporting hypothesis basic architecture universal. Since natural habitat both fluctuations changes microbiome can occur, our work not only illuminates developmental also may guide environmental evolutionary studies by explaining organisms adapt variations.

Язык: Английский

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Balance of activity during a critical period tunes a developing network

eLife, Год журнала: 2023, Номер 12

Опубликована: Окт. 4, 2023

Developing neural circuits are influenced by activity and especially sensitive to changes in during critical periods (CPs) of development. Changes occurring a CP often become 'locked in' so that they affect the mature network. Indeed, several neurodevelopmental disorders have been linked excessive such periods. It is, therefore, important identify those aspects circuit development CP. In this study, we take advantage genetic tractability Drosophila show perturbation an embryonic permanently alters properties locomotor circuit. Specific include increased synchronicity motoneuron greater strengthening excitatory over inhibitory synaptic drive motoneurons. These sufficient reduce network robustness, evidenced sensitivity induced seizure. We also can rescue these when is mitigated inhibition provided mechanosensory neurons. Similarly, demonstrate dose-dependent relationship between experienced extent which it possible hyperexcitable phenotype characteristic parabss mutation. This suggests developing must be exposed properly balanced sum excitation achieve normal function. Our results, provide novel insight into how shapes specific elements circuit, period integrated tune environment will likely

Язык: Английский

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Balance of Activity during a Critical Period Tunes a Developing Network

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 4, 2023

Abstract Developing neural circuits are influenced by activity and especially sensitive to changes in during critical periods (CPs) of development. Changes occurring a CP often become ‘locked-in’ so that they affect the mature network. Indeed, several neurodevelopmental disorders have been linked excessive such periods. It is, therefore, important identify those aspects circuit development CP. In this study, we take advantage genetic tractability Drosophila show perturbation an embryonic permanently alters properties locomotor circuit. Specific include increased synchronicity motoneuron activity, greater strengthening excitatory over inhibitory synaptic drive motoneurons. These sufficient reduce network robustness, evidenced sensitivity induced seizure. We also can rescue these when is mitigated inhibition provided mechanosensory neurons. Similarly, demonstrate dose-dependent relationship between experienced CP, extent which it possible hyperexcitable phenotype characteristic para bss mutation. This suggests developing must be exposed properly balanced sum excitation achieve normal function. Our results, provide novel insight into how shapes specific elements circuit, period integrated tune environment will likely

Язык: Английский

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BK Channels Modulate a Critical Period for Motor Development in Drosophila

Опубликована: Янв. 1, 2023

Critical periods are windows of heightened plasticity occurring during neurodevelopment. Alterations in the excitability neurons these can cause long-lasting changes structure, connectivity, and intrinsic neurons, which may contribute to pathology neurodevelopmental disorders. However, spectrum endogenous regulators critical remains poorly defined. Here we study this issue using a fruit fly (Drosophila) model debilitating early-onset movement disorder caused by BK potassium channel gain-of-function (BK GOF). We develop genetic strategy induce robust expression GOF channels with both spatial temporal control. Using method, show that adult-stage neuronal minimally disrupts movement. In contrast, limiting short window late neurodevelopment profoundly impairs locomotion limb kinematics adult flies. During developmental period, find perturbs synaptic localisation active zone protein Bruchpilot reduces stimulus-independent neurotransmission. Reversing effect enhancing neural activity development rescues motor defects Collectively, our results reveal period for control Drosophila is influenced channels, suggest basis disorders hyperactivity.

Язык: Английский

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A mechanism for tuning proprioception proposed by research in Drosophila and mammals

Exploration of neuroscience, Год журнала: 2024, Номер unknown, С. 27 - 38

Опубликована: Фев. 21, 2024

Proprioception provides important sensory feedback regarding the position of an animal’s body and limbs in space. This interacts with a central pattern generator responsible for rhythmic movement, to adapt locomotion demands that environment places on it. The mechanisms by which this is enabled are poorly understood, belies its importance: dysfunctional proprioception associated movement disorder improving it can help reduce severity symptoms. Similarly, guiding accurate robotic understanding how systems capture process information guide action selection. It therefore interpret research investigates proprioception, ask: what type do proprioceptive sensors capture, they it? Work mammalian models has made progress towards answering question. So too, conducted Drosophila. Fruit fly proprioceptors more accessible than equivalents be manipulated using unique genetic toolkit, so experiments invertebrate make significant contribution overall understanding. difficult, however, relate work different models, draw general conclusions about proprioception. review, therefore, explores fruit revealed proprioceptor function, highlight potential translation mammals. Specifically, present text presents evidence differential expression mechanoelectrical transducers contributes tuning suggests same mechanism may play role proprioceptors.

Язык: Английский

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