Bidirectional control of generalized absence epilepsy networks via real-time direct depolarization of thalamocortical neurons.

Absence seizures (ASs), characterized by bilateral spike-and-wave discharges (SWDs), are a hallmark of idiopathic generalized epilepsies. We investigated the role of thalamocortical (TC) neurons in the generation and termination of ASs using optogenetic techniques in freely behaving GAERS rats, a well-established AS model. We demonstrate that direct depolarization of ChR2-transfected TC neurons in the ventrobasal thalamic nuclei during quiet wakefulness (QW) reliably elicits ethosuximide-sensitive ASs that have similar duration and frequency to those of spontaneous ASs, while showing little and no effect during active wakefulness (AW) and slow wave sleep (SWS), respectively.

Computed tomography reveals hypertrophic remodelling of the diaphragm in cystic fibrosis but not in COPD.

Background: Computed tomography (CT) is increasingly used for assessing skeletal muscle characteristics. In cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), reduced limb muscle mass predicts poor clinical outcomes. However, the degree to which quantity or quality of respiratory and nonrespiratory muscles is affected by these diseases remains controversial.

Layer-specific stimulations of parvalbumin-positive cortical interneurons in mice entrain brain rhythms to different frequencies.

Neocortical interneurons provide inhibition responsible for organizing neuronal activity into brain oscillations that subserve cognitive functions such as memory, attention, or prediction. However, the interneuronal contribution to the entrainment of neocortical oscillations within and across different cortical layers was not described. Here, using layer-specific optogenetic stimulations with micro-Light-Emitting Diode arrays, directed toward parvalbumin-expressing (PV) interneurons in non-anesthetized awake mice, we found that supragranular layer stimulations of PV neurons were most efficient at entraining supragranular local field potential (LFP) oscillations at gamma frequencies (γ: 25-80 Hz), whereas infragranular layer stimulation of PV neurons better entrained the LFP at delta (δ: 2-5 Hz) and theta (θ: 6-10 Hz) frequencies.

HCN channels and absence seizures.

Hyperpolarization-activation cyclic nucleotide-gated (HCN) channels were for the first time implicated in absence seizures (ASs) when an abnormal I (the current generated by these channels) was reported in neocortical layer 5 neurons of a mouse model. Genetic studies of large cohorts of children with Childhood Absence Epilepsy (where ASs are the only clinical symptom) have identified only 3 variants in HCN1 (one of the genes that code for the 4 HCN channel isoforms, HCN1-4), with one (R590Q) mutation leading to loss-of-function. Due to the multi-faceted effects that HCN channels exert on cellular excitability and neuronal network dynamics as well as their modulation by environmental factors, it has been difficult to identify the detailed mechanism by which different HCN isoforms modulate ASs.

Systemic administration of ivabradine, a hyperpolarization-activated cyclic nucleotide-gated channel inhibitor, blocks spontaneous absence seizures.

Objective: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are known to be involved in the generation of absence seizures (ASs), and there is evidence that cortical and thalamic HCN channel dysfunctions may have a proabsence role. Many HCN channel blockers are available, but their role in ASs has been investigated only by localized brain injection or in in vitro model systems due to their limited brain availability. Here, we investigated the effect on ASs of orally administered ivabradine (an HCN channel blocker approved for the treatment of heart failure in humans) following injection of the P-glycoprotein inhibitor elacridar, which is known to increase penetration into the brain of drug substrates for this efflux transporter.

Persephonella atlantica sp. nov.: How to adapt to physico-chemical gradients in high temperature hydrothermal habitats.

A novel thermophilic, microaerophilic and anaerobic, hydrogen- sulphur- and thiosulphate-oxidising bacterium, designated MO1340, was isolated from a deep-sea hydrothermal chimney collected from the Lucky Strike hydrothermal vent field on the Mid-Atlantic Ridge. Cells were short, motile rods of 1.4-2.

Impairments in sensory-motor gating and information processing in a mouse model of haploinsufficiency.

Regulators of chromatin dynamics and transcription are increasingly implicated in the aetiology of neurodevelopmental disorders. Haploinsufficiency of , encoding a histone methyltransferase, is associated with several neurodevelopmental disorders, including Kleefstra syndrome, developmental delay and autism spectrum disorder. Using a mouse model of haploinsufficiency ( ), we examined a number of brain and behavioural endophenotypes of relevance to neurodevelopmental disorders.

Long-term monitoring emphasizes impacts of the dredging on dissolved Cu and Pb contamination along with ultraplankton distribution and structure in Toulon Bay (NW Mediterranean Sea, France).

A long-term monitoring during dredging and non-dredging periods was performed. Total and dissolved Cu and Pb concentrations, DGT-labile Pb, ultraphytoplankton abundance and structure were monitored at four sites: dredging site, dumping site (inside/outside of a geotextile bag) and reference site. During the reference period (non-dredging), an increasing contamination in Pb, Cu and a progressive shift from Synechococcus to photosynthetic picoeukaryotes dominance was observed from reference to dumping site.

Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures.

Absence seizures in children and teenagers are generally considered relatively benign because of their non-convulsive nature and the large incidence of remittance in early adulthood. Recent studies, however, show that 30% of children with absence seizures are pharmaco-resistant and 60% are affected by severe neuropsychiatric comorbid conditions, including impairments in attention, cognition, memory and mood. In particular, attention deficits can be detected before the epilepsy diagnosis, may persist even when seizures are pharmacologically controlled and are aggravated by valproic acid monotherapy.

Compact Optical Neural Probes With Up to 20 Integrated Thin-Film μLEDs Applied in Acute Optogenetic Studies.

This paper reports on the development, characterization and in vivo validation of compact optical neural probes. These novel intracerebral devices comprise micro light-emitting diodes ( μLEDs) integrated along their slender probe shanks with up to 20  μLEDs per device. Blue light with a peak wavelength of 455 nm is emitted from circular apertures 100  μm in diameter.

Gill chamber and gut microbial communities of the hydrothermal shrimp Rimicaris chacei Williams and Rona 1986: A possible symbiosis.

Rimicaris chacei Williams and Rona 1986, formerly named as Chorocaris chacei, is a caridean shrimp living in deep-sea hydrothermal ecosystems. This shrimp is endemic to the Mid Atlantic Ridge (MAR) and lives at the periphery of aggregates of its well-known congeneric R. exoculata Williams and Rona 1986.

Suppression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Function in Thalamocortical Neurons Prevents Genetically Determined and Pharmacologically Induced Absence Seizures.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and the current they generate contribute to the pathophysiological mechanisms of absence seizures (ASs), but their precise role in neocortical and thalamic neuronal populations, the main components of the network underlying AS generation, remains controversial. In diverse genetic AS models, amplitude is smaller in neocortical neurons and either larger or unchanged in thalamocortical (TC) neurons compared with nonepileptic strains. A lower expression of neocortical HCN subtype 1 channels is present in genetic AS-prone rats, and HCN subtype 2 knock-out mice exhibit ASs.

Cortical drive and thalamic feed-forward inhibition control thalamic output synchrony during absence seizures.

Behaviorally and pathologically relevant cortico-thalamo-cortical oscillations are driven by diverse interacting cell-intrinsic and synaptic processes. However, the mechanism that gives rise to the paroxysmal oscillations of absence seizures (ASs) remains unknown. Here we report that, during ASs in behaving animals, cortico-thalamic excitation drives thalamic firing by preferentially eliciting tonic rather than T-type Ca channel (T-channel)-dependent burst firing in thalamocortical (TC) neurons and by temporally framing thalamic output via feedforward reticular thalamic (NRT)-to-TC neuron inhibition.

Dual function of thalamic low-vigilance state oscillations: rhythm-regulation and plasticity.

During inattentive wakefulness and non-rapid eye movement (NREM) sleep, the neocortex and thalamus cooperatively engage in rhythmic activities that are exquisitely reflected in the electroencephalogram as distinctive rhythms spanning a range of frequencies from <1 Hz slow waves to 13 Hz alpha waves. In the thalamus, these diverse activities emerge through the interaction of cell-intrinsic mechanisms and local and long-range synaptic inputs. One crucial feature, however, unifies thalamic oscillations of different frequencies: repetitive burst firing driven by voltage-dependent Ca spikes.

Hybrid intracerebral probe with integrated bare LED chips for optogenetic studies.

This article reports on the development, i.e., the design, fabrication, and validation of an implantable optical neural probes designed for in vivo experiments relying on optogenetics.

Role for serotonin2A (5-HT2A) and 2C (5-HT2C) receptors in experimental absence seizures.

Absence seizures (ASs) are the hallmark of childhood/juvenile absence epilepsy. Monotherapy with first-line anti-absence drugs only controls ASs in 50% of patients, indicating the need for novel therapeutic targets. Since serotonin family-2 receptors (5-HT2Rs) are known to modulate neuronal activity in the cortico-thalamo-cortical loop, the main network involved in AS generation, we investigated the effect of selective 5-HT2AR and 5-HT2CR ligands on ASs in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well established polygenic rat model of these non-convulsive seizures.

Dynamic Analysis of the Conditional Oscillator Underlying Slow Waves in Thalamocortical Neurons.

During non-REM sleep the EEG shows characteristics waves that are generated by the dynamic interactions between cortical and thalamic oscillators. In thalamic neurons, low-threshold T-type Ca(2+) channels play a pivotal role in almost every type of neuronal oscillations, including slow (< 1 Hz) waves, sleep spindles and delta waves. The transient opening of T channels gives rise to the low threshold spikes (LTSs), and associated high frequency bursts of action potentials, that are characteristically present during sleep spindles and delta waves, whereas the persistent opening of a small fraction of T channels, (i.

Competing Mechanisms of Gamma and Beta Oscillations in the Olfactory Bulb Based on Multimodal Inhibition of Mitral Cells Over a Respiratory Cycle.

Gamma (∼40-90 Hz) and beta (∼15-40 Hz) oscillations and their associated neuronal assemblies are key features of neuronal sensory processing. However, the mechanisms involved in either their interaction and/or the switch between these different regimes in most sensory systems remain misunderstood. Based on in vivo recordings and biophysical modeling of the mammalian olfactory bulb (OB), we propose a general scheme where OB internal dynamics can sustain two distinct dynamic states, each dominated by either a gamma or a beta regime.

[Outpatient cannabis withdrawal programme].

Cannabis is the most consumed illicit substance in France, and its use can lead to dependency. Lille university hospital, le Pari association, offers patients wanting to stop using cannabis a support therapy based on positive feedback led by nurses, as well as symptomatic treatment of anxiety and sleep disorders.

The thalamocortical network as a single slow wave-generating unit.

During non-REM sleep the EEG is dominated by slow waves which result from synchronized UP and DOWN states in the component neurons of the thalamocortical network. This review focuses on four areas of recent progress in our understanding of these events. Thus, it has now been conclusively demonstrated that the full expression of slow waves, both of natural sleep and anesthesia, requires an essential contribution by the thalamus.

Investigating local and long-range neuronal network dynamics by simultaneous optogenetics, reverse microdialysis and silicon probe recordings in vivo.

Background: The advent of optogenetics has given neuroscientists the opportunity to excite or inhibit neuronal population activity with high temporal resolution and cellular selectivity. Thus, when combined with recordings of neuronal ensemble activity in freely moving animals optogenetics can provide an unprecedented snapshot of the contribution of neuronal assemblies to (patho)physiological conditions in vivo. Still, the combination of optogenetic and silicone probe (or tetrode) recordings does not allow investigation of the role played by voltage- and transmitter-gated channels of the opsin-transfected neurons and/or other adjacent neurons in controlling neuronal activity.