The structural basis of long-term potentiation in hippocampal synapses, revealed by EM-imaging of lanthanum-induced synaptic vesicle recycling DOI Creative Commons

John E. Heuser

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: April 25, 2022

ABSTRACT Hippocampal neurons in tissue-culture were exposed to the trivalent cation lanthanum for short periods (15 30 minutes) and prepared electron microscopy (EM), evaluate stimulatory effects of this on synaptic ultrastructure. Not only characteristic ultrastructural changes exaggerated vesicle turnover seen within presynapses these cultures - including depletion proliferation vesicle-recycling structures but overall architecture a large proportion synapses was dramatically altered, due postsynaptic ‘bulges’ or herniations into presynapses. Moreover, most cases protrusions produced by EM distort break ‘perforate’ so-called densities (PSD’s) that harbor receptors recognition-molecules essential function. These dramatic EM-observations lead us postulate such PSD-breakages ‘perforations’ could very possibly create substrates ‘tags’ growth, simply creating fragmented free-edges around PSD’s, which new be recruited more easily, thus they represent physical substrate important synaptic-growth process known as “long-term potentiation” (LTP). All created hippocampal tissue-cultures, pushing recycling way beyond its normal limits with lanthanum; we argue report fundamental given can occur at all also extremes neuronal activity, are presumed learning memory.

Language: Английский

Stimulated emission depletion microscopy DOI
Gražvydas Lukinavičius, Jonatan Alvelid, Rūta Gerasimaitė

et al.

Nature Reviews Methods Primers, Journal Year: 2024, Volume and Issue: 4(1)

Published: Aug. 8, 2024

Language: Английский

Citations

19
Extracellular vesicles ameliorates sleep deprivation induced anxiety-like behavior and cognitive impairment in mice DOI Creative Commons

Yiqin Lin,

Zhen-Ming Kang,

Changsheng Su

et al.

Molecular Therapy — Methods & Clinical Development, Journal Year: 2024, Volume and Issue: 32(1), P. 101207 - 101207

Published: Feb. 5, 2024

The aim of this research was to explore the therapeutic capabilities extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) that had been subjected heat shock pretreatment, in treating psychiatric disorders induced by sleep deprivation mice. EVs were isolated and characterized, while western blotting utilized assess expression exosomal markers protein 70 (HSP70). To evaluate impact EV treatment on anxiety-like behavior cognitive impairment sleep-deprived (SD) mice, open field test, plus maze Y-maze task conducted. Heat pretreatment significantly increased HSP70 EVs. Administration shock-pretreated hUC-MSCs improved function SD Furthermore, promoted synaptic expression, inhibited neuroinflammation hippocampus Western analysis also revealed reduced levels TLR4 p65 hippocampus. have potential for deprivation-induced regulating

Language: Английский

Citations

8
Getting sharper: the brain under the spotlight of super-resolution microscopy DOI Creative Commons
Misa Arizono, Agata Idziak,

Federica Quici

et al.

Trends in Cell Biology, Journal Year: 2022, Volume and Issue: 33(2), P. 148 - 161

Published: July 26, 2022

Language: Английский

Citations

24
Super-Resolution Microscopy Opens New Doors to Life at the Nanoscale DOI Creative Commons
Martin Fuhrmann,

Nala Gockel,

Misa Arizono

et al.

Journal of Neuroscience, Journal Year: 2022, Volume and Issue: 42(45), P. 8488 - 8497

Published: Nov. 9, 2022

Super-resolution fluorescence microscopy holds tremendous potential for discovery in neuroscience. Much of the molecular machinery and anatomic specializations that give rise to unique bewildering electrochemical activity neurons are nanoscale by design, ranging somewhere between 1 nm μm. It is at this scale where most unknown exciting action cell biologists flock their dreams, but it was off limits light until recently. While optical principles super-resolution firmly established now, technology continues advance rapidly many crucial areas, enhancing its performance reliability, making more accessible user-friendly, which sorely needed. Indeed, techniques nowadays widely used visualizing immunolabeled protein distributions fixed or living cells. However, a great neuroscience lies shining on structures biochemical activities live-tissue settings, should be developed harnessed much fully. In review, we will present several vivid examples based STED RESOLFT microscopy, illustrating possibilities challenges nano-imaging vivo pique interest tech-developers neurobiologists alike. We cover recent technical progress facilitating applications, share new biological insights into mechanisms cellular communication glia.

Language: Английский

Citations

24
Plasticity of postsynaptic nanostructure DOI Creative Commons
Wouter J. Droogers, Harold D. MacGillavry

Molecular and Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 124, P. 103819 - 103819

Published: Jan. 30, 2023

The postsynaptic density (PSD) of excitatory synapses is built from a wide variety scaffolding proteins, receptors, and signaling molecules that collectively orchestrate synaptic transmission. Seminal work over the past decades has led to identification functional characterization many PSD components. In contrast, we know far less about how these constituents are assembled within synapses, this organization contributes synapse function. Notably, recent evidence high-resolution microscopy studies in silico models, highlights importance precise subsynaptic structure for controlling strength Even further, activity-driven changes distribution glutamate receptors acknowledged contribute long-term efficacy. Thus, defining mechanisms drive structural important molecular understanding transmission plasticity. Here, review current literature on organized mediate basal activity alters nanoscale sustain strength.

Language: Английский

Citations

16
Cognitive synaptopathy: synaptic and dendritic spine dysfunction in age-related cognitive disorders DOI Creative Commons
Francisco J. Barrantes

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Oct. 3, 2024

Cognitive impairment is a leading component of several neurodegenerative and neurodevelopmental diseases, profoundly impacting on the individual, family, society at large. pathologies are driven by multiplicity factors, from genetic mutations risk neurotransmitter-associated dysfunction, abnormal connectomics level local neuronal circuits broader brain networks, to environmental influences able modulate some endogenous factors. Otherwise healthy older adults can be expected experience degree mild cognitive impairment, which fall into category subjective deficits in clinical practice, while many diseases course with more profound alterations cognition, particularly within spectrum dementias. Our knowledge underlying neuropathological mechanisms root this ample palette entities far complete. This review looks current synaptic modifications context function along ageing dysfunction disease, providing insight differential diagnostic elements wide range synapse alterations, those associated changes physiological senescence abnormalities occurring advanced stages dementia. I propose term "cognitive synaptopathy" encompass higher disorders.

Language: Английский

Citations

4
Quantitative Fluorescence Analysis Reveals Dendrite-Specific Thalamocortical Plasticity in L5 Pyramidal Neurons during Learning DOI Creative Commons
Ajit Ray, Joseph A. Christian, Matthew B. Mosso

et al.

Journal of Neuroscience, Journal Year: 2022, Volume and Issue: 43(4), P. 584 - 600

Published: Dec. 12, 2022

High-throughput anatomic data can stimulate and constrain new hypotheses about how neural circuits change in response to experience. Here, we use fluorescence-based reagents for presynaptic postsynaptic labeling monitor changes thalamocortical synapses onto different compartments of layer 5 (L5) pyramidal (Pyr) neurons somatosensory (barrel) cortex from mixed-sex mice during whisker-dependent learning (Audette et al., 2019). Using axonal fills molecular-genetic tags synapse identification fixed tissue Rbp4-Cre transgenic mice, found that the higher-order posterior medial thalamic nucleus showed rapid morphologic both structures at earliest stages sensory association training. Detected increases synaptic size were compartment specific, occurring selectively proximal dendrites L5 Pyr not inputs their apical tufts L1. Both dendritic transient, normalizing back baseline as animals became expert task. Anatomical measurements corroborated by electrophysiological recordings Thus, analysis input- target-specific reveal compartment-specific properties learning. SIGNIFICANCE STATEMENT Synaptic underlie cellular basis learning, experience, neurologic diseases. Neuroanatomical methods assess plasticity provide critical spatial information necessary building models neuronal computations experience but are technically fiscally intensive. describe a confocal fluorescence microscopy–based analytical method input, cell type, location-specific assay. Our only confirms prior allows us predict functional strength pathway-specific manner. findings also indicate primary cortices early Fluorescence-based be an efficient easily adopted approach study variety experimental paradigms.

Language: Английский

Citations

16
Pre- and postsynaptic nanostructures increase in size and complexity after induction of long-term potentiation DOI Creative Commons

Valérie Clavet-Fournier,

ChungKu Lee,

Waja Wegner

et al.

iScience, Journal Year: 2023, Volume and Issue: 27(1), P. 108679 - 108679

Published: Dec. 7, 2023

Synapses, specialized contact sites between neurons, are the fundamental elements of neuronal information transfer. Synaptic plasticity involves changes in synaptic morphology and number neurotransmitter receptors, is thought to underlie learning memory. However, it not clear how these structural functional connected. We utilized time-lapse super-resolution STED microscopy organotypic hippocampal brain slices cultured neurons visualize nano-organization postsynaptic scaffolding protein PSD95, presynaptic Bassoon, GluA2 subunit AMPA receptors by chemically induced long-term potentiation (cLTP) at level single synapses. found that all three proteins increased complexity size after cLTP induction. The increase was largely synchronous, peaking ∼60 min stimulation. Therefore, both individual pre- post-synaptic nanostructures serve as substrates for tuning determining strength.

Language: Английский

Citations

9
Molecular insights into enriched environments and behavioral improvements in autism: a systematic review and meta-analysis DOI Creative Commons
Yutong Li, Jing Lu, Jing Zhang

et al.

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 1, 2024

Aims Autism is a multifaceted developmental disorder of the nervous system, that necessitates novel therapeutic approaches beyond traditional medications and psychosomatic therapy, such as appropriate sensory integration training. This systematic mapping review aims to synthesize existing knowledge on enriching environmental interventions an alternative avenue for improving autism, guiding future research practice. Method A comprehensive search using terms ASD Enriched Environment was conducted across PubMed, EMBASE, ISI, Cochrane, OVID databases. Most literature included in this derived from animal model experiments, with particular focus assessing effect EE autism-like behavior, along related pathways molecular mechanisms. Following extensive group discussion screening, total 19 studies were analysis. Results exhibited potential induce both behavioral biochemical changes, ameliorating behaviors models. These improvements attributed targeting BDNF-related pathways, enhanced neurogenesis, regulation glial inflammation. Conclusion paper underscores positive impact enriched autism through literature. The findings contribute deeper understanding underlying brain mechanisms associated intervention.

Language: Английский

Citations

2
Two-factor synaptic consolidation reconciles robust memory with pruning and homeostatic scaling DOI Creative Commons
Georgios Iatropoulos, Wulfram Gerstner, Johanni Brea

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 24, 2024

Memory consolidation involves a process of engram reorganization and stabilization that is thought to occur primarily during sleep through combination neural replay, homeostatic plasticity, synaptic maturation, pruning. From computational perspective, however, this remains puzzling, as it unclear how the underlying mechanisms can be incorporated into common mathematical model learning memory. Here, we propose solution by deriving uses replay two-factor synapses store memories in recurrent networks with sparse connectivity maximal noise robustness. The offers unified account experimental observations consolidation, such multiplicative scaling, task-driven pruning, increased stimulus selectivity, preferential strengthening weak memories. further predicts intrinsic scales sublinearly strength; supported meta-analysis published imaging datasets.

Language: Английский

Citations

2