Biology subjects

Robert, B.

Publications and source records attributed to Robert, B..

3 recordsLinked to original sources

bioRxiv2020

Flotillin-upregulation acts as an epithelial-mesenchymal transition driver by promoting sphingosine kinase 2-dependent AXL stabilization

Altered endocytosis and vesicular trafficking are major players during tumorigenesis. Flotillin overexpression, a feature observed in many invasive tumors, and identified as a marker of poor prognosis, induces a deregulated endocytic and trafficking pathway called Upregulated Flotillin-Induced Trafficking (UFIT). Here, we found that, in non tumoral mammary epithelial cells, induction of the UFIT pathway promotes epithelial-to-mesenchymal transition (EMT) and accelerates the endocytosis of several transmembrane receptors, including AXL, in flotillin-positive late endosomes. AXL overexpression, frequently observed in cancer cells, is linked to EMT and metastasis formation. In flotillin-overexpressing non-tumoral mammary epithelial cells and in invasive breast carcinoma cells, we found that the UFIT-pathway-mediated AXL endocytosis allows its stabilization and depends on sphingosine-kinase 2, a lipid kinase recruited in flotillin-rich plasma membrane-domains and endosomes. Thus, the deregulation of vesicular trafficking following flotillin upregulation, and through sphingosine kinase 2, emerges as a new mechanism of AXL overexpression and EMT-inducing signaling pathway activation.

cell biology↗

bioRxiv2019

Spatiotemporal patterns of transcranial electrical stimulation can strengthen the metamemory of individual episodic memories in humans

Targeted memory reactivation (TMR) during slow-wave oscillations (SWOs) in non-rapid eye movement (NREM) sleep has been demonstrated with sensory cues to achieve about 5-12% improvement in post-nap memory performance on simple laboratory tasks. But prior work has neither addressed the one-shot aspect of episodic memory acquisition, nor dealt with the presence of interference from ambient environmental cues in real-world settings for the sensory cues. Moreover, TMR with sensory cues may not be scalable to the multitude of experiences over ones lifetime. We designed a novel non-invasive paradigm that tags one-shot experiences of minute-long naturalistic episodes within immersive virtual reality (VR) with unique spatiotemporal amplitude-modulated patterns (STAMPs) of transcranial electrical stimulation (tES) and cues them during SWOs. In particular, we demonstrate that these STAMPs can be re-applied as brief pulses to temporally coincide with UP states of SWOs (0.4167 - 1 s) on two consecutive nights to achieve about 20% improvement in the metamemory of targeted episodes at 48 hours after the one-shot viewing, compared to the control episodes. Post-sleep metamemory of the targeted episodes was driven by an interaction between their pre-sleep metamemory and the number of STAMP applications for those episodes during sleep. Overnight metamemory improvements were mediated by spectral power increases from 6.18 to 6.7 s following the offset of STAMPs in the slow-spindle band (9-12 Hz) for left temporal areas in the scalp electroencephalography (EEG) during sleep. These results prescribe an optimal strategy to leverage STAMPs for boosting metamemory and suggest that real-world episodic memories can be modulated in a targeted manner even with coarser, non-invasive spatiotemporal stimulation.

neuroscience↗

bioRxiv2019

The cholinergic basal forebrain links sensory stimuli with delayed reinforcement to support learning

Linking stimuli with delayed reinforcement requires neural circuits that can bridge extended temporal gaps. Auditory cortex (ACx) circuits reorganize to support auditory fear learning, but only when afferent sensory inputs temporally overlap with cholinergic reinforcement signals. Here we show that mouse ACx neurons rapidly reorganize to support learning, even when sensory and reinforcement cues are separated by a long gap. We found that cholinergic basal forebrain neurons bypass the temporal delay through multiplexed, short-latency encoding of sensory and reinforcement cues. At the initiation of learning, cholinergic neurons in Nucleus Basalis increase responses to conditioned sound frequencies and increase functional connectivity with ACx. By rapidly scaling up responses to sounds that predict reinforcement, cholinergic inputs jump the gap to align with bottom-up sensory traces and support associative cortical plasticity.

neuroscience↗