Ground state depletion microscopy as a tool for studying microglia–synapse interactions

Paasila, Patrick Jarmo; Fok, Sandra; Flores‐Rodriguez, Neftali; Sajjan, Sujata; Svahn, Adam J.; Dennis, Claude; Holsinger, R. M. Damian; Kril, Jillian J.; Becker, Thomas; Bánati, Richard B.; Sutherland, Greg T.; Graeber, Manuel B.

doi:10.1002/jnr.24819

Cited by 7 publications

(8 citation statements)

References 80 publications

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“…Thus, we demonstrate that PL from BNNPs can be enhanced by MSD. The obtained result for the proposed BNNPs can be useful for nanoscopic applications, for example, in the ground-state depletion (GSD) microscopy. ,, …”

Section: Resultsmentioning

confidence: 92%

“…The obtained result for the proposed BNNPs can be useful for nanoscopic applications, for example, in the ground-state depletion (GSD) microscopy. 40,65,66 We believe that the proposed h-BN nanoparticles may find application in single-molecule localization microscopy (SMLM), which uses blinking fluorescent objects to overcome the diffraction limit. 27,67 When nonblinking emitters are required, our results may also be of interest because emitters may blink less (which is not true for any nanoparticle) when coexcited.…”

Section: Photocontrol With Coexcitationmentioning

confidence: 99%

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Photocontrol of Single-Photon Generation in Boron Nitride Nanoparticles: Implications for Quantum Photon Sources, Sub-Diffraction Nanoscopy, and Bioimaging

Gritsienko

Matveev

Kurochkin

et al. 2022

ACS Appl. Nano Mater.

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Hexagonal boron nitride (h-BN) is a promising material for nanophotonics. Intrinsic and artificially induced defects in h-BN films, flakes, and nanoparticles are potential candidates as quantum emitters at room temperature. However, the energy structure and the methods for controlling these defects are still unclear. In this paper, we have obtained single-photon sources in ultrafine h-BN nanoparticles fabricated by a cost-effective ammonothermal dehydration. We demonstrate quantum-dot-like emission using photon autocorrelation and fluorescence intensity trace measurements in the red range. The results obtained using low-power near-ultraviolet coexcitation reveal the distinctive photophysical properties of fluorescent defects in the synthesized h-BN nanoparticles. We show that quantum emitters in nanoparticles can be switched from dark to bright mode by coexcitation photocontrol. The observed effects in nanoparticles were explained by various mechanisms of metastable state disabling. We also report a 2-fold improvement in the contrast of fluorescence images from h-BN nanoparticles under low-intensity laser scanning coexcitation. The research results can be used to develop efficient solid-state photon sources, as well as in nanoscopy employing biocompatible fluorescent nanoparticles.

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Section: Resultsmentioning

confidence: 92%

Section: Photocontrol With Coexcitationmentioning

confidence: 99%

Photocontrol of Single-Photon Generation in Boron Nitride Nanoparticles: Implications for Quantum Photon Sources, Sub-Diffraction Nanoscopy, and Bioimaging

Gritsienko

Matveev

Kurochkin

et al. 2022

ACS Appl. Nano Mater.

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“…However, the total percentage of microglia associated with a cluster was <2% and only a minority of Aβ plaques were associated with a cluster—the proportion of which decreased in a stepwise fashion from mildly to severely affected regions. Lastly, the internalisation of synaptophysin-positive pre-synapses was found to be significantly elevated in the superior frontal cortex of AD cases compared to both CAc and controls without AD-type pathology using super-resolution microscopy ( Paasila et al, 2021 ). Synaptophysin is one of the most severely affected synaptic markers in AD ( Reddy et al, 2005 ).…”

Section: Microglia In Alzheimer’s Diseasementioning

confidence: 99%

“…More recently in AD, microglia have been shown to internalise greater quantities of synaptic material during the symptomatic phase of the disease. This has been demonstrated using confocal ( Tzioras et al, 2019 ) and single-molecule localisation microscopy ( Paasila et al, 2021 ) of archival cortical tissue samples.…”

Section: Introductionmentioning

confidence: 99%

Synapses, Microglia, and Lipids in Alzheimer’s Disease

et al. 2022

Self Cite

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Alzheimer’s disease (AD) is characterised by synaptic dysfunction accompanied by the microscopically visible accumulation of pathological protein deposits and cellular dystrophy involving both neurons and glia. Late-stage AD shows pronounced loss of synapses and neurons across several differentially affected brain regions. Recent studies of advanced AD using post-mortem brain samples have demonstrated the direct involvement of microglia in synaptic changes. Variants of the Apolipoprotein E and Triggering Receptors Expressed on Myeloid Cells gene represent important determinants of microglial activity but also of lipid metabolism in cells of the central nervous system. Here we review evidence that may help to explain how abnormal lipid metabolism, microglial activation, and synaptic pathophysiology are inter-related in AD.

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“…The procedure they described opens the spectrum of molecular imaging using antibodies and SR microscopy to the analysis of routine formalin-fixed paraffin sections of the archival human brain. Especially interesting is the investigation of microglia-synapse interactions in dementia [115].…”

Section: Super-resolution Imagingmentioning

confidence: 99%

Digging Deeper: Advancements in Visualization of Inhibitory Synapses in Neurodegenerative Disorders

Radulović

Sunkara

Maurer

et al. 2021

IJMS

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Recent research has provided strong evidence that neurodegeneration may develop from an imbalance between synaptic structural components in the brain. Lately, inhibitory synapses communicating via the neurotransmitters GABA or glycine have come to the center of attention. Increasing evidence suggests that imbalance in the structural composition of inhibitory synapses affect deeply the ability of neurons to communicate effectively over synaptic connections. Progressive failure of synaptic plasticity and memory are thus hallmarks of neurodegenerative diseases. In order to prove that structural changes at synapses contribute to neurodegeneration, we need to visualize single-molecule interactions at synaptic sites in an exact spatial and time frame. This visualization has been restricted in terms of spatial and temporal resolution. New developments in electron microscopy and super-resolution microscopy have improved spatial and time resolution tremendously, opening up numerous possibilities. Here we critically review current and recently developed methods for high-resolution visualization of inhibitory synapses in the context of neurodegenerative diseases. We present advantages, strengths, weaknesses, and current limitations for selected methods in research, as well as present a future perspective. A range of new options has become available that will soon help understand the involvement of inhibitory synapses in neurodegenerative disorders.

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Ground state depletion microscopy as a tool for studying microglia–synapse interactions

Cited by 7 publications

References 80 publications

Photocontrol of Single-Photon Generation in Boron Nitride Nanoparticles: Implications for Quantum Photon Sources, Sub-Diffraction Nanoscopy, and Bioimaging

Photocontrol of Single-Photon Generation in Boron Nitride Nanoparticles: Implications for Quantum Photon Sources, Sub-Diffraction Nanoscopy, and Bioimaging

Synapses, Microglia, and Lipids in Alzheimer’s Disease

Digging Deeper: Advancements in Visualization of Inhibitory Synapses in Neurodegenerative Disorders

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