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Andrianarivelo, A., Stein, H., Gabillet, J. et al. Cerebellar activity is triggered by reach endpoint during learning of a complex locomotor task. Nat Commun (2026). https://doi.org/10.1038/s41467-026-74823-1 

Find this information on the CNRS Biology website

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Salla disease is a rare genetic disorder with no current treatment, causing motor delay, and intellectual disability. Its cause lies in mutation of a transporter protein called sialin that is able to transport certain sugars from the interior of the cell organelles called lysosomes to their exterior. One of the most common mutations responsible for the disease is R39C, where one amino acid is swapped for another. This slight change leads to an interruption of the correct functioning of the transporter though how it does this has remained unknown so far. 

In a new study recently released as a preprint, the Membrane Dynamics team at SPPIN, in collaboration with Dassault Systèmes BIOVIA, proposes a mechanistic answer to this question. 

Sialin works as a rocker-switch, opening alternately toward the lysosome and the cytosol. Combining Molecular Dynamics simulations, evolutionary analysis and mutagenesis, the authors identified two key structural features: an interaction triplet (R39, E194, E262) acting as a modulator, and an ionic lock (K197–D350) holding the protein open toward the lysosome. In healthy sialin, the triplet periodically weakens the lock, allowing the switch to flip. In the R39C mutation, the triplet is no longer present leaving the lock permanently engaged and the sugars that would be transported under normal conditions trapped inside lysosomes. 

Beyond fundamental understanding of how the transporter works in healthy individuals, this work is the first to provide a molecular level understanding of how Salla disease is caused. The research was supported by the Salla Treatment And Disease foundation, the Dassault Systèmes foundation and the Vaincre les maladies lysosomales foundation.

Reference: https://doi.org/10.64898/2026.04.20.719580 

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The new study ¹ reveals that subcellular localization of Importin β1 plays a crucial role in memory by supporting local translation at neuronal synapses. While Importin β1 is best known for transporting molecules into the nucleus, this work shows it is also essential at CNS presynaptic terminals, far from the cell body.

Using a mouse model in which Importin β1 could no longer properly localize to axons, they found clear impairments in hippocampus-dependent spatial and contextual memory. These deficits were traced to specific synapses in the hippocampus, where a presynaptic form of long-term plasticity (LTP) was disrupted.

At the molecular level, loss of axonal Importin β1 led to changes in synaptic protein composition and reduced local translation of key presynaptic components. As a result, synapses had fewer neurotransmitter vesicles ready for release, weakening communication between neurons.

These findings highlight the importance of local protein synthesis in maintaining synaptic function and memory, and identify Importin β1 as a key player in this process. The study opens new avenues for understanding how neurons regulate communication across long distances in the brain.

P.A Freund/N. Panayotis. et al.Science Signaling, 2026 (10.1126/scisignal.ady2026)

• Link to the paper: https://www.science.org/doi/10.1126/scisignal.ady2026
• Link to a summary (IN FRENCH) by UPCité: https://u-paris.fr/le-transport-subcellulaire-au-service-de-la-memoire/
• Link to a summary (IN FRENCH) by CNRS Biologie: https://www.insb.cnrs.fr/fr/cnrsinfo/le-transport-subcellulaire-au-service-de-la-memoire

1. Thisresearch is the result of long-standing collaborative efforts from the Fainzilber lab (Weizmann Institute of Science, Rehovot, Israel) where Nicolas worked before joining the SPPIN as a group leader in 2023, the Kreutz Lab (Leibniz Institute for Neurobiology, Magdeburg, Germany), the Burlingame lab (UCSF), and the Kawaguchi team (UCLA) in the US. ︎

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This paper set out to answer a fundamental question in motor learning: How do our brains adapt and learn new movements so quickly? We trained mice to use a joystick to retrieve rewards. To test their adaptation, we imposed a sudden perturbation (a 2x gain; lower panel in the video) that they needed to overcome. Remarkably, much like humans adapting to force-field or visuomotor perturbations, the mice adjusted their movements in only a few pulls.

This speed poses a challenge for classic supervised learning models. Climbing fibers provide error signals to Purkinje cells, but these signals are traditionally viewed as binary: error vs no error. How can such a coarse signal drive rapid, precise behavioral adaptation?

By imaging complex spikes in populations of Purkinje cells during learning, we found the answer in the collective activity.. Bands of cells responded similarly, and together these groups transformed the binary error/no-error signal into something far richer, encoding both the magnitude and direction of the behavioral error.

Although the error from a single pull produces only minuscule LTD/LTP at individual synapses, the combined effect across the population is strong enough to influence the very next joystick movement.

If you prefer a visual walkthrough over reading the paper, Brandon Stell explains the full results and the story here: https://www.youtube.com/watch?v=rNQYOyjr6SI

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Congratulation to Floriane ESHAK and Francine ACHER (team 4) for the cover of Journal of Chemical Information and Modeling.

Article :

Epitope Identification of an mGlu5 Receptor Nanobody Using Physics-Based Molecular Modeling and Deep Learning Techniques. Eshak F, Pion L, Scholler P, Nevoltris D, Chames P, Rondard P, Pin JP, Acher FC, Goupil-Lamy A : J Chem Inf Model, 2024

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Recent progress has boosted the resolving power of optical microscopies to spatial dimensions well below the diffraction limit. Yet, axial super-resolution and axial single-molecule localisation typically require more complicated implementations than their lateral counterparts. Also, there is a lack of suitable calibration tools that would permit a facile metrology along the microscope’s optical axis. Axial test samples are also needed for quantifying nanometric drift, or axial fluorophore mobility, or again for quantifying the sub-wavelength light confinement in near-field microscopies. In our work work, submitted to Opt Commun and now available as a preprint on arXiv, we propose a simple solution for axial metrology by translating an axial metrology challenge into a spectral imaging and mixing problem, by aid of a multi-layered single-excitation, dual-emission test slide, in which axial distance is colour-encoded. 

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Total internal reflection and other near-field optical techniques excel in selectively imaging dynamic processes at or near the basal plasma membrane, e.g., single-receptor or single-vesicle dynamics. However, it has been difficult to quantify TIRF intensities and relate them to axial fluorophore distance. Now, in Klimovsk et al. researchers from SPPIN’s team1 and the Salomon’s Lab at Bar-Ilan University describe a simple optical technique for simultaneously characterising the refractive index, flurophore distance and field-homogeneity of evanescent-wave excited thin fluorophore films. Test samples were assembled by combining “nanosandwiches” of thin (<200 nm) spacer layer made from a bioimimetic polymer and thin dye layers. Using such test slides with different thickness, they could quantify the flurophore distance with <10 nm resolution. The technique is based on the detection in the far-field and the analysis of the fluorphore radiation pattern in the back-focal plane of a high-NA objective.

NANOSCALE project web site

Characterizing nanometric thin films with far-field light, Hodaya Klimovsky, Omer Shavit, Carine Julien, Ilya Olevsko, Mohamed Hamode, Yossi Abulafia, Hervé Suaudeau, Vincent Armand, Martin Oheim, Adi Salomon, Advanced Optical Materials, 2022.08.15.503956; doi: https://doi.org/10.1101/2022.08.15.503956

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A group of researchers around Adi Salomon (BINA Nanocenter, Ramat-Gan, Israel) and Martin Oheim (SPPIN) have developed a simple nanometric calibration tool for axial super-resolution imaging. In a pre-print available on biorXiv, they describe a simple, non-invasive, optical technique for simultaneously characterizing the refractive index, thickness, and homogeneity of nanometric transparent layers. In the case of the calibration sample, these layers are made of the biomimetic polymer, My-133-MC, having a refractive index of 1.33, so as to approach the cytosol for biological applications. The technique is based on the detection in the far field and the analysis of supercritical angle fluorescence (SAF), i.e., near-field emission from molecular dipoles located very close to the dielectric interface. Applications to localising FM-dye labelled vesicles in cortical astrocytes are presented.

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