Objective: Animal and human studies have shown that the seizure-generating region is vastly dependent on distant neuronal hubs that can decrease duration and propagation of ongoing seizures. However, we still lack a comprehensive understanding of the impact of distant brain areas on specific interictal and ictal epileptic activities (e.g.
View Article and Find Full Text PDFStudying the development of brain network disruptions in epilepsy is challenged by the paucity of data before epilepsy onset. Here, we used the unilateral, kainate mouse model of hippocampal epilepsy to investigate brain network changes before and after epilepsy onset and their stability across time. Using 32 epicranial electrodes distributed over the mouse hemispheres, we analyzed EEG epochs free from epileptic activity in 15 animals before and 28 days after hippocampal injection (group 1) and in 20 animals on two consecutive days (d28 and d29, group 2).
View Article and Find Full Text PDFNeuronal excitation imposes a high demand of ATP in neurons. Most of the ATP derives primarily from pyruvate-mediated oxidative phosphorylation, a process that relies on import of pyruvate into mitochondria occuring exclusively via the mitochondrial pyruvate carrier (MPC). To investigate whether deficient oxidative phosphorylation impacts neuron excitability, we generated a mouse strain carrying a conditional deletion of MPC1, an essential subunit of the MPC, specifically in adult glutamatergic neurons.
View Article and Find Full Text PDFGNAO1 encephalopathy characterized by a wide spectrum of neurological deficiencies in pediatric patients originates from de novo heterozygous mutations in the gene encoding Gαo, the major neuronal G protein. Efficient treatments and even the proper understanding of the underlying etiology are currently lacking for this dominant disease. Adequate animal models of GNAO1 encephalopathy are urgently needed.
View Article and Find Full Text PDFObjective: In patients with epilepsy, interictal epileptic discharges are a diagnostic hallmark of epilepsy and represent abnormal, so-called "irritative" activity that disrupts normal cognitive functions. Despite their clinical relevance, their mechanisms of generation remain poorly understood. It is assumed that brain activity switches abruptly, unpredictably, and supposedly randomly to these epileptic transients.
View Article and Find Full Text PDFErythropoietin (EPO), the hypoxia-inducible hematopoietic hormone, has well-established neuroprotective/neurotrophic roles in the developing central nervous system and the therapeutic potential of EPO has been widely explored in clinical studies for the treatment of perinatal hypoxic brain lesion, as well as prematurity. Here, we reveal that both EPO and Epo receptor (EPOR) are expressed in the developing rat somatosensory cortex during radial migration and laminar positioning of granular and supragranular neurons. Experimental deregulation of EPO signaling using genetic approaches results in aberrant migration, as well as permanent neuronal misplacement leading to abnormal network activity and protracted sensory behavioral deficits.
View Article and Find Full Text PDFTransplantation of appropriate neuronal precursors after injury is a promising strategy to reconstruct cortical circuits, but the efficiency of these approaches remains limited. Here, we applied targeted apoptosis to selectively ablate layer II/III pyramidal neurons in the rat juvenile cerebral cortex and attempted to replace lost neurons with their appropriate embryonic precursors by transplantation. We demonstrate that grafted precursors do not migrate to replace lost neurons but form vascularized clusters establishing reciprocal synaptic contacts with host networks and show functional integration.
View Article and Find Full Text PDFThe amplitude of the brain response to a repeated auditory stimulus is diminished as compared to the response to the first tone (T1) for interstimulus intervals (ISI) lasting up to hundreds of milliseconds. This adaptation process, called auditory sensory gating (ASG), is altered in various psychiatric diseases including schizophrenia and is classically studied by focusing on early evoked cortical responses to the second tone (T2) using 500-ms ISI. However, mechanisms underlying ASG are still not well-understood.
View Article and Find Full Text PDFLarge-scale brain networks are increasingly recognized as important for the generation of seizures in epilepsy. However, how a network evolves from a healthy state through the process of epileptogenesis remains unclear. To address this question, here, we study longitudinal epicranial background EEG recordings (30 electrodes, EEG free from epileptiform activity) of a mouse model of mesial temporal lobe epilepsy.
View Article and Find Full Text PDFLarge-scale slow oscillations allow the integration of neuronal activity across brain regions during sensory or cognitive processing. However, evidence that this form of coding also holds for pathological networks, such as for distributed networks in epileptic disorders, does not yet exist. Here, we show in a mouse model of unilateral hippocampal epilepsy that epileptic fast ripples generated in the neocortex distant from the primary focus occur during transient trains of interictal epileptic discharges.
View Article and Find Full Text PDFSensory processing continues during sleep and can influence brain oscillations. We previously showed that a gentle rocking stimulation (0.25 Hz), during an afternoon nap, facilitates wake-sleep transition and boosts endogenous brain oscillations (i.
View Article and Find Full Text PDFIn the version of this article initially published, the right panel in Fig. 2b was duplicated from the corresponding panel in Fig. 2c, and some data points in Fig.
View Article and Find Full Text PDFMost research on focal epilepsy focuses on mechanisms of seizure generation in the primary epileptic focus (EF). However, neurological deficits that are not directly linked to seizure activity and that may persist after focus removal are frequent. The recruitment of remote brain regions of an epileptic network (EN) is recognized as a possible cause, but a profound lack of experimental evidence exists concerning their recruitment and the type of pathological activities they exhibit.
View Article and Find Full Text PDFThe coordinated propagation of activity across cortical layers enables simultaneous local computation and inter-areal interactions. A pattern of upward propagation from deeper to more superficial layers, which has been repeatedly demonstrated in spontaneous activity, would allow these functions to occur in parallel. But it remains unclear whether upward propagation also occurs for stimulus evoked activity, and how it relates to activity in other cortical areas.
View Article and Find Full Text PDFPerturbed neuronal migration and circuit development have been implicated in the pathogenesis of neurodevelopmental diseases; however, the direct steps linking these developmental errors to behavior alterations remain unknown. Here we demonstrate that Wnt/C-Kit signaling is a key regulator of glia-guided radial migration in rat somatosensory cortex. Transient downregulation of Wnt signaling in migrating, callosal projection neurons results in delayed positioning in layer 2/3.
View Article and Find Full Text PDFLong-term consolidation of memories depends on processes occurring many hours after acquisition. Whether this involves plasticity that is specifically required for long-term consolidation remains unclear. We found that learning-induced plasticity of local parvalbumin (PV) basket cells was specifically required for long-term, but not short/intermediate-term, memory consolidation in mice.
View Article and Find Full Text PDFCortical processing of sensory stimuli typically recruits multiple areas, but how each area dynamically incorporates activity from other areas is not well understood. We investigated interactions between cortical columns of bilateral primary sensory regions (S1s) in rats by recording local field potentials and multi-unit activity simultaneously in both S1s with electrodes positioned at each cortical layer. Using dynamic connectivity analysis based on Granger-causal modeling, we found that, shortly after whisker stimulation (< 10 ms), contralateral S1 (cS1) already relays activity to granular and infragranular layers of S1 in the other hemisphere, after which cS1 shows a pattern of within-column interactions that directs activity upwards toward superficial layers.
View Article and Find Full Text PDFHigh-density scalp EEG recordings are widely used to study whole-brain neuronal networks in humans non-invasively. Here, we validate EEG mapping of somatosensory evoked potentials (SSEPs) in macaque monkeys (Macaca fascicularis) for the long-term investigation of large-scale neuronal networks and their reorganisation after lesions requiring a craniotomy. SSEPs were acquired from 33 scalp electrodes in five adult anaesthetized animals after electrical median or tibial nerve stimulation.
View Article and Find Full Text PDFErythropoietin (EPO) has been recognized as a neuroprotective agent. In animal models of neonatal brain injury, exogenous EPO has been shown to reduce lesion size, improve structure and function. Experimental studies have focused on short course treatment after injury.
View Article and Find Full Text PDFTime-varying connectivity methods are increasingly used to study directed interactions between brain regions from electrophysiological signals. These methods often show good results in simulated data but it is unclear to what extent connectivity results obtained from real data are physiologically plausible. Here we introduce a benchmark approach using multichannel somatosensory evoked potentials (SEPs) measured across rat cortex, where the structural and functional connectivity is relatively simple and well-understood.
View Article and Find Full Text PDFLarge-scale neuronal networks integrating several cortical areas mediate the complex functions of the brain such as sensorimotor integration. Little is known about the functional development of these networks and the maturational processes by which distant networks become functionally connected. We addressed this question in the postnatal rat sensorimotor system.
View Article and Find Full Text PDFNeonatal hypoxia-ischemia (HI) is the most important cause of brain injury in the newborn. Here we studied structural alterations and functional perturbations of developing large-scale sensorimotor cortical networks in a rat model of moderate HI at postnatal day 3 (P3). At the morphological level, HI led to a disorganized barrel pattern in the somatosensory cortex without detectable histological changes in the motor cortex.
View Article and Find Full Text PDFThe group I metabotropic glutamate receptor 5 (mGluR5) has been implicated in the development of cortical sensory maps. However, its precise roles in the synaptic function and plasticity of thalamocortical (TC) connections remain unknown. Here we first show that in mGluR5 knockout (KO) mice bred onto a C57BL6 background cytoarchitectonic differentiation into barrels is missing, but the representations for large whiskers are identifiable as clusters of TC afferents.
View Article and Find Full Text PDFMice actively explore their environment by rhythmically sweeping their whiskers. As a consequence, neuronal activity in somatosensory pathways is modulated by the frequency of whisker movement. The potential role of rhythmic neuronal activity for the integration and consolidation of sensory signals, however, remains unexplored.
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