Biology subjects

Geoffroy, H.

Publications and source records attributed to Geoffroy, H..

6 recordsLinked to original sources

bioRxiv2025

Slow Intrinsic Oscillations in the Ventrolateral Preoptic nucleus

The ventrolateral preoptic nucleus (VLPO) of the hypothalamus plays a major role in the induction and consolidation of non-rapid eye movement (NREM) sleep. While VLPO neurons are heterogeneous, they often display low-threshold spikes (LTS), a feature that supports rhythmic activity. Nevertheless, rhythmic bursting in these VLPO neurons has never been observed. Here, we report that [~]12% of VLPO neurons in a large database of ex vivo patch-clamp recordings display spontaneous rhythmic bursting of action potentials. This activity occurred in putative sleep-promoting neurons, identified by inhibitory responses to noradrenaline (NA), as well as wake-active neurons that were activated by NA. Unsupervised clustering of 24 neurons based on burst properties, electrophysiological, and morphological features revealed three distinct groups: one corresponding to putative sleep-promoting neurons and two wake-active neurons with fast and slow bursting dynamics. Strikingly, membrane potential oscillations persisted in the presence of tetrodotoxin (TTX), indicating that rhythmic bursting is driven by intrinsic mechanisms rather than network activity. These findings suggest that rhythmic bursting is an intrinsic and functionally relevant mode of activity in VLPO neurons, which may contribute to sleep regulation.

neuroscience↗

bioRxiv2022

Synergistic stabilization of microtubules by BUB-1, HCP-1 and CLS- 2 controls meiotic spindle assembly in C. elegans oocytes

During cell division, chromosome segregation is orchestrated by a microtubule-based spindle. Interaction between spindle microtubules and kinetochores is central to the bi-orientation of chromosomes. Initially dynamic to allow spindle assembly and kinetochore attachments, which is essential for chromosome alignment, microtubules are eventually stabilized for efficient segregation of sister chromatids and homologous chromosomes during mitosis and meiosis I respectively. Therefore, the precise control of microtubule dynamics is of utmost importance during mitosis and meiosis. Here, we study the assembly and role of a kinetochore module, comprised of the kinase BUB-1, the two redundant CENP-F orthologs HCP-1/2, and the CLASP family member CLS-2 (hereafter termed the BHC module), in the control of microtubule dynamics in Caenorhabditis elegans oocytes. Using a combination of in vivo structure-function analyses of BHC components and in vitro microtubule-based assays, we show that BHC components stabilize microtubules, which is essential for meiotic spindle formation and accurate chromosome segregation. Overall, our results show that BUB-1 and HCP-1/2 do not only act as targeting components for CLS-2 at kinetochores, but also synergistically control kinetochore-microtubule dynamics by promoting microtubule pause. Together, our results suggest that BUB-1 and HCP-1/2 actively participate in the control of kinetochore-microtubule dynamics in the context of the BHC module to promote accurate chromosome segregation in meiosis.

cell biology↗

bioRxiv2021

LACTATE IS A MAJOR ENERGY SUBSTRATE FOR CORTICAL NEURONS AND ENHANCES THEIR FIRING ACTIVITY

Glucose is the mandatory fuel for the brain, yet the relative contribution of glucose and lactate for neuronal energy metabolism is unclear. We found that increased lactate, but not glucose concentration, enhances the spiking activity of neurons of the cerebral cortex. Enhanced spiking was dependent on ATP-sensitive potassium (KATP) channels formed with Kir6.2 and SUR1 subunits, which we show are functionally expressed in most neocortical neuronal types. We also demonstrate the ability of cortical neurons to take-up and metabolize lactate. We further reveal that ATP is produced by cortical neurons largely via oxidative phosphorylation and only modestly by glycolysis. Our data demonstrate that in active neurons, lactate is preferred to glucose as an energy substrate, and that lactate metabolism shapes neuronal activity in the neocortex through KATP channels. Our results highlight the importance of metabolic crosstalk between neurons and astrocytes for brain function. HighlightsO_LIMost cortical neurons subtypes express pancreatic beta-cell like KATP channels. C_LIO_LILactate enhances spiking activity via its uptake and closure of KATP channels. C_LIO_LICortical neurons take up and oxidize lactate. C_LIO_LICortical neurons produce ATP mainly by oxidative phosphorylation. C_LI

neuroscience↗

bioRxiv2018

Dissociation of fear initiation and maintenance by breathing-driven prefrontal oscillations

Does the body play an active role in emotions? Since the original James/Cannon controversy this debate has mainly been fueled by introspective accounts of human experience. Here, we use the animal model to demonstrate a physiological mechanism for bodily feedback and its causal role in the stabilization of emotional states. We report that during fear-related freezing mice breathe at 4Hz and show, using probabilistic modelling, that optogenetic perturbation of this feedback specifically reduces freezing maintenance without impacting its initiation. This rhythm is transmitted by the olfactory bulb to the prefrontal cortex where it organizes neural firing and optogenetic probing of the circuit demonstrates frequency-specific tuning that maximizes prefrontal cortex responsivity at 4Hz, the breathing frequency during freezing. These results point to a brain-body-brain loop in which the initiation of emotional behavior engenders somatic changes which then feedback to the cortex to directly participate in sustaining emotional states.

neuroscience↗

bioRxiv2018

General Regulatory Factors control the fidelity of transcription by restricting non-coding and ectopic initiation

The fidelity of transcription initiation is essential for accurate gene expression, but the determinants of start site selection are not fully understood. Rap1 and other General Regulatory Factors (GRFs) control the expression of many genes in yeast. We show that depletion of these factors induces widespread ectopic transcription initiation within promoters. This generates many novel non-coding RNAs and transcript isoforms with diverse stability, profoundly altering the coding potential of the transcriptome. Ectopic transcription initiation strongly correlates with altered nucleosome positioning. We show that Rap1 sterically constrains nucleosomes as its mere binding to the DNA can be sufficient for restoration normal nucleosome positioning, transcription initiation and gene expression. These results demonstrate an essential role for GRFs in the fidelity of transcription initiation and in the suppression of pervasive transcription, redefining current models of their function. They have general implications for the mechanism of transcription initiation and the control of gene expression.\n\nHIGHLIGHTSO_LIRap1, Abf1 and Reb1 control the fidelity of transcription initiation and suppress pervasive transcription\nC_LIO_LIWidespread ectopic transcription initiation in Rap1-deficient cells induces variegated alterations in gene expression\nC_LIO_LIAltered nucleosome positioning in GRFs-defective cells correlate with ectopic transcription initiation.\nC_LIO_LIRap1 controls nucleosomes positioning and transcription initiation at least partially by a steric hindrance mechanism\nC_LI

genomics↗

bioRxiv2017

Harnessing sleep/wake state tracking by olfactory bulb oscillations to perform fully brain-based sleep scoring in mice

It has long been thought that sleep scoring could not be achieved with brain signals alone despite the deep neuromodulatory transformations that accompany sleep state changes. Here we demonstrate using multi-site electrophysiological LFP recordings in freely moving mice that gamma power in the olfactory bulb (OB) allows for clear classification of sleep and wake. Coupled with hippocampal theta activity, it allows the construction of a sleep scoring algorithm that relies on brain activity alone. This method reaches over 90% homology with classical methods based on muscular activity (EMG) and video tracking. Moreover, contrary to EMG, OB gamma power allows correct discrimination between sleep and immobility in ambiguous situations such as fear-related freezing. We use the instantaneous power of hippocampal theta oscillation and OB gamma oscillation to construct a 2D phase-space that is highly robust across mice and days. Dynamic analysis of trajectories within this space yields a novel characterization of sleep/wake and wake/sleep transitions as deeply divergent phenomena. Whereas waking up is a fast and direct transition, falling asleep is best described as stochastic and gradual change. Altogether this methodology opens the avenue for multi-timescale characterization of sleep states with high temporal resolution based on brain signals only.

neuroscience↗