Biology subjects

Vachon, C.

Publications and source records attributed to Vachon, C..

4 recordsLinked to original sources

bioRxiv2025

An extracellular complex between CLE-1/collagen XV/XVIII and Punctin/MADD-4 defines cholinergic synapse identity

The precise localization of postsynaptic receptors opposite neurotransmitter release sites is essential for synaptic function. This alignment relies on adhesion molecules, intracellular scaffolds, and a growing class of extracellular scaffolding proteins. However, how these secreted proteins are retained at synapses remains unclear. We addressed this question using C. elegans neuromuscular junctions, where Punctin, a conserved extracellular synaptic organizer, positions postsynaptic receptors. We identified CLE-1, the ortholog of collagens XV/XVIII, as a key stabilizer of Punctin. Punctin and CLE-1B, the main isoform present at neuromuscular junctions, form a complex and rely on each other for synaptic localization. Punctin undergoes cleavage, and in the absence of CLE-1, specific fragments are lost, resulting in the mislocalization of cholinergic receptors to GABAergic synapses. Additionally, CLE-1 regulates receptor levels independently of Punctin. These findings highlight a crucial extracellular complex that maintains synapse identity.

neuroscience↗

bioRxiv2021

DAF-2/insulin IGF-1 receptor regulates mobility during ageing by integrating opposite inputs from muscle and neuronal tissues

During ageing, preservation of locomotion is generally considered an indicator of sustained good health, in elderlies and in animal models. In C. elegans, mutants of the insulin-IGF-1 receptor DAF-2/IIRc represent a paradigm of healthy ageing, as their increased lifespan is accompanied by a delay in age-related loss of motility. However, these animals are less mobile than wild-type animals in early adulthood. Here we investigated the DAF-2/IIRc- dependent relationship between longevity and motility using an auxin-inducible degron to trigger tissue-specific degradation of endogenous DAF-2/IIRc. As previously reported, inactivation of DAF-2/IIRc in neurons or intestine was sufficient to extend the lifespan of worms, whereas depletion in epidermis, germline or muscle was not. However, neither intestinal nor neuronal depletion of DAF-2/IIRc prevented the age-related loss of motility. In 1-day-old adults, DAF-2/IIRc depletion in neurons reduced motility in a DAF-16/FOXO dependent manner, while muscle depletion had no effect. By contrast, DAF-2 depletion in the muscle of middleage animals improved their motility independently of DAF-16/FOXO but required UNC-120/SRF. Yet, neuronal or muscle DAF-2/IIRc depletion both preserved the mitochondria network in ageing muscle. Overall, these results show that the motility pattern of daf-2 mutants is determined by the sequential and opposing impact of neurons and muscle tissues and can be dissociated from the regulation of the lifespan. This work also provides the characterization of a versatile tool to analyze the tissue-specific contribution of insulin-like signaling in integrated phenotypes at the whole organism level.

physiology↗

bioRxiv2020

The HSPG Syndecan is a core organizer of cholinergic synapses in C. elegans

The extracellular matrix has emerged as an active component of chemical synapses regulating synaptic formation, maintenance and homeostasis. The heparan sulfate proteoglycan syndecans are known to regulate cellular and axonal migration in the brain. They are also enriched at synapses, but their synaptic functions remain more elusive. Here we show that SDN-1, the sole ortholog of syndecan in C. elegans, is absolutely required for the synaptic clustering of homomeric 7-like N-acetylcholine receptors (AChR) and regulates the synaptic content of heteromeric L-AChRs. SDN-1 is concentrated at neuromuscular junctions (NMJs) by the neurally-secreted synaptic organizer Ce-Punctin/MADD-4, which also activates the transmembrane netrin receptor DCC. Those cooperatively recruit the FARP and CASK orthologues that localize N-AChRs at cholinergic NMJs through physical interactions. Therefore, SDN-1 stands at the core of the cholinergic synapse organization by bridging the extracellular synaptic determinants to the intracellular synaptic scaffold that controls the postsynaptic receptor content.

neuroscience↗

bioRxiv2018

The effects of awareness of the perturbation during motor adaptation on hand localization

Explicit awareness of a task is often evoked during rehabilitation and sports training with the intention of accelerating learning and improving performance. However, the effects of awareness of perturbations on the resulting sensory and motor changes produced during motor learning are not well understood. Here, we use explicit instructions as well as large rotation sizes to generate awareness of the perturbation during a visuomotor rotation task and test the resulting changes in both perceived and predicted sensory consequences as well as implicit motor changes.\n\nWe split participants into 4 groups which differ in both magnitude of the rotation (either 30{degrees} or 60{degrees}) during adaptation, and whether they receive a strategy to counter the rotation or not prior to adaptation. Performance benefits of explicit instruction are largest during early adaptation but continued to lead to improved performance through 90 trials of training. We show that with either instruction, or with large perturbations, participants become aware of countering the rotation. However, we find a base amount of implicit learning, with equal magnitudes, across all groups, even when asked to exclude any strategies while reaching with no visual feedback of the hand.\n\nParticipants also estimate the location of the unseen hand when it is moved by the robot (passive localization) and when they generate their own movement (active localization) following adaptation. These learning-induced shifts in estimates of hand position reflect both proprioceptive recalibration and updates in the predicted consequences of movements. We find that these estimates of felt hand position, which reflect updates in both proprioception and efference based estimates of hand position, shift significantly for all groups and were not modulated by either instruction or perturbation size.\n\nOur results indicate that not all processes of motor learning benefit from an explicit awareness of the task. Particularly, proprioceptive recalibration and the updating of predicted sensory consequences are largely implicit processes.

neuroscience↗