Activity-dependent local protection and lateral inhibition control synaptic competition in developing mitral cells in mice

Developmental Cell, Journal Year: 2023, Volume and Issue: 58(14), P. 1221 - 1236.e7

Published: June 7, 2023

In developing brains, activity-dependent remodeling facilitates the formation of precise neuronal connectivity. Synaptic competition is known to facilitate synapse elimination; however, it has remained unknown how different synapses compete with one another within a post-synaptic cell. Here, we investigate mitral cell in mouse olfactory bulb prunes all but primary dendrite during developmental process. We find that spontaneous activity generated essential. show strong glutamatergic inputs trigger branch-specific changes RhoA pruning remaining dendrites: NMDAR-dependent local signals suppress protect from pruning; subsequent depolarization induces neuron-wide activation prune non-protected dendrites. NMDAR-RhoA are also essential for synaptic barrel cortex. Our results demonstrate general principle whereby lateral inhibition across establishes discrete receptive field neuron.

Language: Английский

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Microglia as hunters or gatherers of brain synapses

Nature Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Language: Английский

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Motion detection: Specific thalamocortical connections revealed

Current Biology, Journal Year: 2025, Volume and Issue: 35(1), P. R11 - R13

Published: Jan. 1, 2025

Language: Английский

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Activity-dependent synaptic competition and dendrite pruning in developing mitral cells

Frontiers in Neural Circuits, Journal Year: 2025, Volume and Issue: 19

Published: Jan. 27, 2025

During the early postnatal period, neurons in sensory circuits dynamically remodel their connectivity to acquire discrete receptive fields. Neuronal activity is thought play a central role circuit remodeling during this period: stabilizes some synaptic connections while eliminating others. Synaptic competition plays binary choice between stabilization and elimination. While activity-dependent “punishment signals” propagating from winner loser synapses have been hypothesized drive synapse elimination, exact nature has remained elusive. In review, I summarize recent studies mouse mitral cells that explain how only one dendrite stabilized others are eliminated, based on spontaneous olfactory bulb. discuss hypothetical punishment signals act but not dendrites establish primary per cell, anatomical basis for odorant receptor-specific parallel information processing

Language: 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, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 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.

Language: Английский

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Reduced GABAergic inhibition and impaired synapse elimination by neuroligin-2 deletion from Purkinje cells of the developing cerebellum

Frontiers in Neural Circuits, Journal Year: 2025, Volume and Issue: 19

Published: March 14, 2025

Functionally mature neural circuits are shaped during postnatal development by eliminating redundant synapses formed around birth. This process is known as synapse elimination and requires a proper balance of excitation inhibition. Neuroligin-2 (NL2) postsynaptic cell adhesion molecule required for the formation, maintenance, function inhibitory synapses. However, how NL2 regulates largely unknown. Here we report that deletion from Purkinje cells (PCs) in cerebellum impairs developmental climbing fiber (CF) to PC In global NL2-knockout (KO) mice, GABAergic inhibition PCs was attenuated CF impaired after day 10 (P10). These phenotypes were restored expression into NL2-KO mice. Moreover, microRNA-mediated knockdown specifically caused elimination. innervated "strong" "weak" CFs, calcium transients elicited CFs enhanced NL2-deficient PCs, suggesting excess signaling permits survival We conclude crucial maintaining synaptic properly development.

Language: Английский

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Activity-dependent synapse elimination requires caspase-3 activation

Published: March 20, 2025

During brain development, synapses are initially formed in excess and later eliminated an activity-dependent manner. Weak preferentially removed, but the mechanism linking neuronal activity to synapse removal is unclear. Here we show that, developing mouse visual pathway, inhibiting synaptic transmission induces postsynaptic activation of caspase-3. Caspase-3 deficiency results defects elimination driven by both spontaneous experience-dependent neural activity. Notably, caspase-3 blocks elimination, as evidenced reduced engulfment inactive microglia. Furthermore, a model Alzheimer’s disease, protects against loss induced amyloid-β deposition. Our reveal key step during development neurodegeneration.

Language: Английский

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Microglia Are Dispensable for Developmental Dendrite Pruning of Mitral Cells in Mice

eNeuro, Journal Year: 2023, Volume and Issue: 10(11), P. ENEURO.0323 - 23.2023

Published: Oct. 27, 2023

Abstract During early development, neurons in the brain often form excess synaptic connections. Later, they strengthen some connections while eliminating others to build functional neuronal circuits. In olfactory bulb, a mitral cell initially extends multiple dendrites glomeruli but eventually forms single primary dendrite through activity-dependent pruning process. Recent studies have reported that microglia facilitate synapse during circuit remodeling systems. It has remained unclear whether are involved developing brains. Here, we examined required for developmental of cells mice. To deplete fetal brain, treated mice with colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622, from pregnancy. Microglia were reduced by >90% PLX5622. However, was not significantly affected. Moreover, found no significant differences number, density, and size excitatory synapses formed dendrites. We also evidence role layer 4 (L4) barrel cortex. contrast, density (dendritic spines) granule bulb increased PLX5622 at postnatal day (P) 6, suggesting regulation dendritic spines. Our results indicate do play critical neurite level development

Language: Английский

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Activity-Dependent Synapse Refinement: From Mechanisms to Molecules

The Neuroscientist, Journal Year: 2023, Volume and Issue: 30(6), P. 673 - 689

Published: May 4, 2023

The refinement of immature neuronal networks into efficient mature ones is critical to nervous system development and function. This process synapse driven by the activity–dependent competition converging synaptic inputs, resulting in elimination weak inputs stabilization strong ones. Neuronal activity, whether form spontaneous activity or experience-evoked known drive numerous brain regions. More recent studies are now revealing manner mechanisms which detected converted molecular signals that appropriately regulate weaker synapses stronger Here, we highlight how evoked instruct during refinement. We then focus on transformed cues determine execute A comprehensive understanding underlying can lead novel therapeutic strategies neuropsychiatric diseases characterized aberrant

Language: Английский

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Synapse Weakening-Induced Caspase-3 Activity Confers Specificity to Microglia-Mediated Synapse Elimination

Published: Sept. 25, 2024

During brain development, synapses are initially formed in excess and later eliminated an activity-dependent manner, with weak being preferentially removed. Previous studies identified glia as mediators of synapse removal, but it is unclear how specifically target synapses. Here we show that, the developing mouse visual pathway, inhibiting synaptic transmission induces postsynaptic activation caspase-3. Caspase-3 essential for elimination driven by both spontaneous experience-dependent neural activity. Synapse weakening-induced caspase-3 determines specificity mediated microglia not astrocytes. Furthermore, a model Alzheimer’s disease, deficiency protects against loss induced amyloid-β deposition. Our results reveal key step during development neurodegeneration.

Language: Английский

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