Biology subjects

Deschenes, M.

Publications and source records attributed to Deschenes, M..

3 recordsLinked to original sources

bioRxiv2025

Proof-of-principle of NF1 Gene Therapy in plexiform neurofibroma mice models

Neurofibromatosis type I is a rare neurocutaneous syndrome characterized by the development of disfiguring neurofibroma tumors with unmet clinical needs. As Neurofibromatosis Type I is a monogenic disease, the development of gene therapy is highly attractive, but it is currently unknown if rescuing the NF1 gene in established neurofibroma is sufficient for tumor regression. Here, we test this hypothesis by building two novel NF1 mouse models with reversible NF1 expression. In the first model, the human NF1 -/- Schwann cells named ipNF95.11b were genetically modified with a doxycycline-inducible full-length mouse Nf1 gene. One month after cells implantation in the sciatic nerve, mice were split into 2 groups. Strikingly, all sciatic nerves from mice allowed to drink doxycycline water for one month display complete normalization of the sciatic nerve histologically (n=6 sciatic nerves) whereas 83% (5 out of 6 sciatic nerves) develop or maintain a neurofibroma when drinking regular water. In the second model, the human NF1 +/- Schwann cells named ipNF95.11c were genetically modified with a doxycycline-inducible potent shRNA against the NF1 mRNA transcript. Strikingly, doxycycline withdrawal after neurofibroma establishment allowed complete normalization (n=4 sciatic nerves), whereas all sciatic nerves showed evidence of neurofibroma when kept on doxycycline (n=4 sciatic nerves). Thus, we proof-of-principle NF1 Gene Therapy in plexiform neurofibroma mice models.

cancer biology↗

bioRxiv2021

Cortex-independent open-loop control of a voluntary orofacial motor action

Whether using our eyes or our hands, we interact with our environment through mobile sensors. The efficient use of these sensory organs implies the ability to track their position; otherwise, perceptual stability and prehension would be profoundly impeded1,2. The nervous system may be informed about the position of a sensory organ via two complementary feedback mechanisms: peripheral reafference (external, sensory feedback) and efference copy (internal feedback)3-6. Yet, the potential contributions of these mechanisms remain largely unexplored. By training rats to place their vibrissae within a predetermined angular range without contact, a task that depends on knowledge of vibrissa position relative to their face, we found that peripheral reafference is not required. The presence of motor cortex is not required either, even in the absence of peripheral reafference. On the other hand, the red nucleus, which receives descending inputs from motor cortex and the cerebellum and projects to facial motoneurons7-10, is critical for the execution of the vibrissa task. All told, our results demonstrate the existence of an open-loop control by an internal model that is sufficient to drive voluntary motion. The internal model is independent of motor cortex and likely contains the cerebellum and associated nuclei.

neuroscience↗

bioRxiv2021

A vibrissa pathway that activates the limbic system

Vibrissa sensory inputs play a central role in driving rodent behavior. These inputs transit through the sensory trigeminal nuclei, which give rise to the ascending lemniscal and paralemniscal pathways. While lemniscal projections are somatotopically mapped from brain stem to cortex, those of the paralemniscal pathway are more widely distributed. Yet the extent and topography of paralemniscal projections are unknown, along with the potential role of these projections in controlling behavior. Here we used viral tracers to map paralemniscal projections. We find that this pathway broadcasts vibrissa-based sensory signals to brain stem regions that are involved in the regulation of autonomic functions and to forebrain regions that are involved in the expression of emotional reactions. We further provide evidence that GABAergic cells of the Kolliker-Fuse nucleus gate trigeminal sensory input in the paralemniscal pathway via a mechanism of presynaptic or extrasynaptic inhibition.

neuroscience↗