Filopodia are a structural substrate for silent synapses in adult neocortex

Nature, Journal Year: 2022, Volume and Issue: 612(7939), P. 323 - 327

Published: Nov. 30, 2022

Language: Английский

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Synaptic Mechanisms Regulating Mood State Transitions in Depression

Annual Review of Neuroscience, Journal Year: 2022, Volume and Issue: 45(1), P. 581 - 601

Published: May 4, 2022

Depression is an episodic form of mental illness characterized by mood state transitions with poorly understood neurobiological mechanisms. Antidepressants reverse the effects stress and depression on synapse function, enhancing neurotransmission, increasing plasticity, generating new synapses in stress-sensitive brain regions. These properties are shared to varying degrees all known antidepressants, suggesting that synaptic remodeling could play a key role pathophysiology antidepressant function. Still, it unclear whether precisely how synaptogenesis contributes transitions. Here, we review evidence supporting emerging model which defined distinct distributed across multiple circuits, neurons assuming altered functional properties, configurations, and, importantly, reduced capacity for plasticity adaptation. act initially facilitating enabling reconfiguration this state. Subsequently, plays specific sustaining these changes over time.

Language: Английский

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Binary and analog variation of synapses between cortical pyramidal neurons

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2019, Volume and Issue: unknown

Published: Dec. 31, 2019

Abstract Learning from experience depends at least in part on changes neuronal connections. We present the largest map of connectivity to date between cortical neurons a defined type (L2/3 pyramidal cells), which was enabled by automated analysis serial section electron microscopy images with improved handling image defects. used identify constraints learning algorithms employed cortex. Previous studies modeled continuum synapse sizes (Arellano et al. 2007) log-normal distribution (Loewenstein, Kuras, and Rumpel 2011; de Vivo 2017; Santuy 2018). A is consistent most neural network models learning, synaptic strength continuously graded analog variable. Here we show that size, when restricted synapses L2/3 cells, well-modeled sum binary variable an drawn distribution. Two sharing same presynaptic postsynaptic cells are known be correlated size (Sorra Harris 1993; Koester Johnston 2005; Bartol 2015; Kasthuri Dvorkin Ziv 2016; Bloss 2018; Motta 2019). variables two highly correlated, while not. Binary variation could outcome Hebbian or other plasticity rule depending activity signals relatively uniform across arbors, may dominated influences. discuss implications for stability-plasticity dilemma.

Language: Английский

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Isochronic development of cortical synapses in primates and mice

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 4, 2023

Abstract The neotenous, or delayed, development of primate neurons, particularly human ones, is thought to underlie primate-specific abilities like cognition. We tested whether synaptic follows suit—would synapses, in absolute time, develop slower longer-lived, highly cognitive species non-human primates than shorter-lived with less human-like abilities, e.g., the mouse? Instead, we find that excitatory and inhibitory synapses male Mus musculus (mouse) Rhesus macaque (primate) cortex form at similar rates, times after birth. Primate mouse also prune such an isochronic fashion. Mouse are lone exception, which not pruned instead continuously added throughout life. monotony clocks across disparate lifespans, experiences, argues programs likely orchestrated by genetic events rather experience.

Language: Английский

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Structural neural plasticity evoked by rapid-acting antidepressant interventions

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

Published: Nov. 18, 2024

Language: Английский

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Neuropathogenic role of astrocyte‐derived extracellular vesicles in HIV‐associated neurocognitive disorders

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(4)

Published: April 1, 2024

Abstract Our previous findings demonstrated that astrocytic HIF‐1α plays a major role in HIV‐1 Tat‐mediated amyloidosis which can lead to Alzheimer's‐like pathology‐a comorbidity of HIV‐Associated Neurocognitive Disorders (HAND). These amyloids be shuttled extracellular vesicles, and we sought assess whether Tat stimulated astrocyte‐derived EVs (ADEVs) containing the toxic could result neuronal injury vitro vivo. We thus hypothesized blocking likely mitigate Tat‐ADEV‐mediated injury. Rat hippocampal neurons when exposed Tat‐ADEVs carrying exhibited amyloid accumulation synaptodendritic injury, leading functional loss as evidenced by alterations miniature excitatory post synaptic currents. The silencing not only reduced biogenesis ADEVs, well cargos, but also ameliorated synaptodegeneration. Next, determined effect hippocampus naive mice brains. Naive receiving Tat‐ADEVs, behavioural changes, Alzheimer's ’s‐like pathology accompanied This impairment(s) was observed injected with silenced ADEVs. is first report demonstrating amyloid‐carrying ADEVs mediating synaptodegeneration changes associated HAND highlights protective HIF‐1α.

Language: Английский

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SpineTool is an open-source software for analysis of morphology of dendritic spines

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: June 29, 2023

Abstract Dendritic spines form most excitatory synaptic inputs in neurons and these are altered many neurodevelopmental neurodegenerative disorders. Reliable methods to assess quantify dendritic morphology needed, but existing subjective labor intensive. To solve this problem, we developed an open-source software that allows segmentation of from 3D images, extraction their key morphological features, classification clustering. Instead commonly used spine descriptors based on numerical metrics chord length distribution histogram (CLDH) approach. CLDH method depends lengths chords randomly generated within volume. achieve less biased analysis, a procedure uses machine-learning algorithm experts’ consensus machine-guided clustering tool. These approaches unbiased automated measurements, should provide useful resource for variety neuroscience research applications.

Language: Английский

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Dendritic spine morphology regulates calcium-dependent synaptic weight change

The Journal of General Physiology, Journal Year: 2022, Volume and Issue: 154(8)

Published: July 12, 2022

Dendritic spines act as biochemical computational units and must adapt their responses according to activation history. Calcium influx acts the first signaling step during postsynaptic is a determinant of synaptic weight change. also come in variety sizes shapes. To probe relationship between calcium dynamics spine morphology, we used stochastic reaction-diffusion model idealized realistic geometries. We show that despite nature various channels, receptors, pumps, size shape can modulate subsequently updates deterministic manner. Through series exhaustive simulations analyses, found change depend on volume-to-surface area spine. The relationships morphology identified geometries hold geometries, suggesting there are geometrically determined may

Language: Английский

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Selective activation of BK channels in small‐headed dendritic spines suppresses excitatory postsynaptic potentials

The Journal of Physiology, Journal Year: 2022, Volume and Issue: 600(9), P. 2165 - 2187

Published: Feb. 23, 2022

Dendritic spines are the main receptacles of excitatory information in brain. Their particular morphology, with a small head connected to dendrite by slender neck, has inspired theoretical and experimental work understand how these structural features affect processing, storage integration synaptic inputs pyramidal neurons (PNs). The activation glutamate receptors triggers large voltage change as well calcium signals at spine head. Thus, voltage-gated calcium-activated potassium channels located likely play key role transmission. Here we study presence function conductance (BK) from layer 5 PNs. We found that BK localized dendrites regardless their size, but activity can only be detected volumes (≤0.09 μm3 ), which reduces amplitude two-photon uncaging postsynaptic potentials recorded soma. In addition, significantly larger than those observed volumes. accordance our data, numerical simulations predict impinging onto generate responses within itself volumes, sufficient activate channels. These results show selectively activated small-headed spines, suggesting new level dendritic spine-mediated regulation plasticity cortical KEY POINTS: expressed visual cortex neuron somata, size. (2P) (EPSPs) Two-photon imaging revealed intracellular 2P-activated ) showed suppress EPSPs.

Language: Английский

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Structural Analysis of Human and Mouse Dendritic Spines Reveals a Morphological Continuum and Differences across Ages and Species

eNeuro, Journal Year: 2022, Volume and Issue: 9(3), P. ENEURO.0039 - 22.2022

Published: May 1, 2022

Dendritic spines have diverse morphologies, with a wide range of head and neck sizes, these morphologic differences likely generate different functional properties. To explore how this diversity differs across species ages we analyzed 3D confocal reconstructions ∼8000 human ∼1700 mouse spines, labeled by intracellular injections in fixed tissue. Using unsupervised algorithms, computationally separated spine heads necks systematically measured features apical basal dendrites from cortical pyramidal cells. Human had unimodal distributions parameters, without any evidence subtypes. Their were longer thinner than volumes an 85-year-old individual larger those 40-year-old individual. thicker spines. Our results indicate that form part continuum, are mice, become increasing adult age. These could biochemical electrical compartmentalization, or synaptic properties, ages.

Language: Английский

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