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Cordelieres, F. P.

Publications and source records attributed to Cordelieres, F. P..

4 recordsLinked to original sources

Long-term quality assessment and monitoring of light microscope performance through accessible and reliable protocols, tools and metrics

Reliable, reproducible and comparable results are what biology requires from microscopy. To achieve that level of confidence, monitoring the stability of the microscope performance over time with standardized quality testing routines is essential for mining quantitative data. Three levels of microscope quality control procedures should be considered: i) usage of accessible and affordable tools and samples, ii) execution of easy and fast, preferably automatized, acquisition protocols, iii) analysis of data in the most automated way possible with adequate metrics for long-term monitoring. In this paper, we test the acquisition protocols on the mainly used microscope techniques (wide-field, spinning disk and confocal microscopy) with simple quality control tools. Seven protocols specify metrics on measuring the lateral and axial resolution (Point-Spread Function) of the system, field flatness, chromatic aberrations and co-registration, illumination power monitoring and stability, stage drift and positioning repeatability and finally temporal and spatial noise sources of camera detectors. We designed an ImageJ/FiJi java plugin named MetroloJ_QC to incorporate the identified metrics and automatize the data processing for the analysis. After processing and comparing the data of microscopes from more than ten imaging facilities, we test the robustness of the metrics and the protocols by determining experimental limit values. Our results give a first extensive characterization of the quality control procedures of a light microscope, with an automated data processing and experimental limit values that can be used by core facility staff and researchers to monitor the microscope performance over time.

scientific communication and education↗

Synaptic and supra-synaptic organisation of the dopaminergic projection to the striatum.

Dopamine is a monoamine involved in reward processing and motor control. Volume transmission is thought to be the mechanism by which monoamines modulate effector systems at glutamate and GABA synapses. Hence, dopamine synapses are scarcely described. We applied fluorescence activated synaptosome sorting to explore the features of the dopaminergic synaptome. We provide the proteome of striatal dopaminergic synapses with 57 proteins specifically enriched. Beyond canonical markers of dopamine neurotransmission (Th, Slc6a3/DAT, Slc18a2/VMAT2), we validated 6 proteins belonging to pre- and postsynaptic sides (Cpne7, Apba1/Mint1, Cadps2, Cadm2/SynCAM 2, Stx4 and Mgll). Moreover, dopaminergic varicosities adhere to both a post-synapse with cognate receptors and glutamatergic, GABAergic or cholinergic synapses in structures we named dopaminergic "hub synapses". Markers of presynaptic vesicles and active zone, post-synaptic density and spine apparatus, are significantly increased upon association with dopamine inputs in hubs. Thus neuromodulation frequently operates from hub synapses affecting associated synapses and is not solely dependent on volume transmission. Finally, FASS provides a new framework for the exploration of dopaminergic synapses and more generally for discrete synapse populations ex-vivo. HighlightsO_LIA first proteome of dopaminergic synapses in the striatum C_LIO_LIStriatal dopaminergic synaptosomes display post-synaptic cognate receptors C_LIO_LIDopaminergic projections build hub synapses with excitatory, inhibitory, and cholinergic projections. C_LIO_LICortico-striatal synaptic scaffolds are strengthened upon association in hub synapses. C_LI

neuroscience↗

Mammalian vesicular glutamate transporter VGLUT1 reduces synaptic vesicle superpool size and spontaneous release frequency.

Glutamate secretion at excitatory synapses is tightly regulated to allow for the precise tuning of synaptic strength. Vesicular Glutamate Transporters (VGLUT) accumulate glutamate into synaptic vesicles (SV) and thereby regulate quantal size. Further, the number of release sites and the release probability of SVs maybe regulated by the organization of active zone proteins and SV clusters. In the present work, we uncover a mechanism mediating an increased SV clustering through a tripartite interaction of VGLUT1, endophilinA1 and intersectin1. This strengthening of SV clusters results in a combined reduction of axonal SV super-pool size and miniature excitatory events frequency. Our findings support a model in which clustered vesicles are held together through multiple weak interactions between SH3 domains and proline rich sequences of synaptic proteins. In mammals, VGLUT1 gained a poly-proline sequence that recruits endophilinA1 and turns the transporter into a dual regulator of quantal release parameters at excitatory synapses.

neuroscience↗

Uncoupling Intraflagellar Transport and Primary Cilia Formation Demonstrates Deep Integration of IFT in Hedgehog Signaling

The vertebrate hedgehog pathway is organized in primary cilia and hedgehog components relocate into or out of cilia during signaling. Defects in intraflagellar transport (IFT) typically disrupt ciliary assembly and attenuate hedgehog signaling. Determining if IFT drives the movement of hedgehog components is difficult due to the requirement of IFT for building cilia. Unlike most IFT proteins, IFT27 is dispensable for cilia formation but affects hedgehog signaling similar to other IFTs allowing us to examine its role in the dynamics of signaling. Activating signaling at points along the pathway in Ift27 mutant cells showed that IFT is extensively involved in the pathway. Similar analysis of Bbs mutant cells showed that BBS proteins participate at many levels of signaling but are not needed to concentrate Gli transcription factors at the ciliary tip. Our analysis showed that smoothened delivery to cilia does not require IFT27, but the role of other IFTs is not known. Using a rapamycin-induced dimerization system to stop IFT after ciliary assembly was complete we show that smoothened delivery to cilia is IFT independent.\n\nAbbreviations

cell biology↗