Biology subjects

Leinekugel, X.

Publications and source records attributed to Leinekugel, X..

4 recordsLinked to original sources

bioRxiv2025

Parallel emergence of perisomatic inhibition and ripples in the developing hippocampal circuit

During hippocampal Sharp Wave Ripples, sequences of awake coding activities are replayed with a rhythmic timing and high level of synchrony favorable for synaptic plasticity and transfer of information to downstream structures. Previous work reported the emergence of ripples at P10 in the CA1 region, together with the development of inhibition. On the other hand, neither the relationships between perisomatic inhibition and ripples nor their developmental emergence have been investigated in CA3, in which ripples have a different frequency profile (90-110Hz instead of 140-200Hz in CA1), functional perisomatic inhibitory circuits have different properties, and some developmental aspects such as neurogenesis or interneuron maturation are early compared to CA1. We have here investigated the hypothesis of a conjoint and earlier appearance and maturation of ripples and perisomatic inhibition in the CA3 hippocampal region compared to CA1. We report a parallel sequence of events in CA3 and CA1, starting with the early expression of perisomatic GABAergic synaptic activity combined with the emergence of ripple activity. Interestingly, perisomatic inhibition and ripple activity follow parallel maturation trajectories, beginning in CA3 at P7 with immature (i.e. not functional yet) inhibition and immature ripples (proto-ripples) with labile oscillatory frequency. Mature functional perisomatic inhibition and clear high-frequency ripple activity progressively emerge between P10 and P12, reaching adult-like properties by P13. A similarly progressive maturation of ripples occurs in CA1, from P11 to P15. The progressive emergence of functional inhibition and specific patterns of neuronal activity likely support the progressive emergence of cognitive function to which they are necessary prerequisite.

neuroscience↗

bioRxiv2020

Detecting fine and elaborate movements with piezo sensors, from heartbeat to the temporal organization of behavior

Behavioral phenotyping devices have been successfully used to build ethograms, but studying the temporal dynamics of individual movements during spontaneous, ongoing behavior, remains a challenge. We now report on a novel device, the Phenotypix, which consists in an open-field platform resting on highly sensitive piezoelectric (electro-mechanical) pressure-sensors, with which we could detect the slightest movements from freely moving rats and mice. The combination with video recordings and signal analysis based on time-frequency decomposition, clustering and machine learning algorithms allowed to quantify various behavioral components with unprecedented accuracy, such as individual heartbeats and breathing cycles during rest, shaking in response to pain or fear, and the dynamics of balance within individual footsteps during spontaneous locomotion. We believe that this device represents a significant progress and offers new opportunities for the awaited advance of behavioral phenotyping.

animal behavior and cognition↗

bioRxiv2019

Intrinsic neuronal excitability and spontaneous activity underlie cortical abnormalities upon Nr2f1/COUP-TFI deficiency

The formation of functional cortical maps in the cerebral cortex results from a timely regulated interaction between intrinsic genetic mechanisms and electrical activity. To understand how transcriptional regulation influences network activity and neuronal excitability within the neocortex, we used mice deficient for the area mapping gene Nr2f1 (also known as COUP-TFI), a key determinant of somatosensory area specification during development. We found that cortical loss of Nr2f1 impacts on spontaneous network activity and synchronization at perinatal stages. In addition, we observed alterations in the intrinsic excitability and morphological features of layer V pyramidal neurons. Accordingly, we identified distinct voltage-gated ion channels regulated by Nr2f1 that might directly influence intrinsic bioelectrical properties during critical time windows of somatosensory cortex specification. Together, our data suggest a tight link between Nr2f1 and neuronal excitability in the developmental sequence that ultimately sculpts the emergence of cortical network activity within the immature neocortex.

neuroscience↗

bioRxiv2019

Probing the polarity of GABAergic transmission in vivo

Several studies suggest a contribution of reversed, excitatory GABA to epileptogenesis. But GABAergic transmission critically depends on the very dynamic combination of membrane potential, conductance and occurrence of other synaptic inputs. Taking this complexity into account implies measuring the postsynaptic responses to spontaneously occurring GABAergic events, in vivo, without interfering with neuronal [Cl-]i. Because of technical difficulties, this has not been achieved yet. We have overcome this challenge by combining in vivo extracellular detection of both optogenetically-evoked and spontaneously occurring unitary inhibitory postsynaptic field-potentials (fIPSPs), with the silicon probe recording of neuronal firing activity, with single cell resolution. We report that isolated acute seizures induced a global reversal of the polarity of CA3 hippocampal GABAergic transmission, shifting from inhibitory to excitatory for a duration of several tens of seconds before returning to normal polarity. Nevertheless we observed this reversed polarity only in the post-ictal period during which neurons (including GABAergic interneurons) were silent. Perisomatic inhibition was also affected during the course of epileptogenesis in the Kainate model of chronic epilepsy. One week after Kainate injection, the majority of pyramidal cells escaped inhibitory control by perisomatic GABAergic events. Besides, we did not observe a reversed polarity of fIPSPs, but fIPSPs provided time-locked excitation to a minor subset of CA3 pyramidal neurons. Beside methodological interests, our results suggest that subtle alterations in the regulation of [Cl-]i and perisomatic GABAergic transmission already operate in the hippocampal circuit during the latent period that precedes the establishment of chronic epilepsy.

neuroscience↗