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Brian P Grone, Tiange Qu, Scott C Baraban
Loss-of-function mutations in SCN1A cause Dravet syndrome (DS), a catastrophic childhood epilepsy in which patients experience comorbid behavioral conditions, including movement disorders, sleep abnormalities, anxiety, and intellectual disability. To study the functional consequences of voltage-gated sodium channel mutations, we use zebrafish with a loss-of-function mutation in scn1lab, a zebrafish homolog of human SCN1A. Homozygous scn1lab(s552/s552) mutants exhibit early-life seizures, metabolic deficits, and early death...
July 2017: ENeuro
(no author information available yet)
[This corrects the article DOI: 10.1523/ENEURO.0015-17.2017.][This corrects the article DOI: 10.1523/ENEURO.0015-17.2017.].
July 2017: ENeuro
Christophe Bernard
No abstract text is available yet for this article.
July 2017: ENeuro
Amanda L York, James Q Zheng
The neuromuscular junction (NMJ) is a chemical synapse formed between motoneurons and skeletal muscle fibers. The vertebrate NMJ uses acetylcholine (ACh) as the neurotransmitter and features numerous invaginations of the postsynaptic muscle membrane termed junctional folds. ACh receptors (AChRs) are believed to be concentrated on the crest of junctional folds but their spatial organization remains to be fully understood. In this study, we utilized super-resolution microscopy to examine the nanoscale organization of AChRs at NMJ...
July 2017: ENeuro
Mercè Cases, Artur Llobet, Beatrice Terni, Inmaculada Gómez de Aranda, Marta Blanch, Briain Doohan, Alexander Revill, Angus M Brown, Juan Blasi, Carles Solsona
ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood-brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system...
July 2017: ENeuro
Shireene Kalbassi, Sven O Bachmann, Ellen Cross, Victoria H Roberton, Stéphane J Baudouin
In most mammals, including humans, the postnatal acquisition of normal social and nonsocial behavior critically depends on interactions with peers. Here we explore the possibility that mixed-group housing of mice carrying a deletion of Nlgn3, a gene associated with autism spectrum disorders, and their wild-type littermates induces changes in each other's behavior. We have found that, when raised together, male Nlgn3 knockout mice and their wild-type littermates displayed deficits in sociability. Moreover, social submission in adult male Nlgn3 knockout mice correlated with an increase in their anxiety...
July 2017: ENeuro
Melissa Lau, Jianli Li, Hollis T Cline
The neurovascular niche is a specialized microenvironment formed by the interactions between neural progenitor cells (NPCs) and the vasculature. While it is thought to regulate adult neurogenesis by signaling through vascular-derived soluble cues or contacted-mediated cues, less is known about the neurovascular niche during development. In Xenopus laevis tadpole brain, NPCs line the ventricle and extend radial processes tipped with endfeet to the vascularized pial surface. Using in vivo labeling and time-lapse imaging in tadpoles, we find that intracardial injection of fluorescent tracers rapidly labels Sox2/3-expressing NPCs and that vascular-circulating molecules are endocytosed by NPC endfeet...
July 2017: ENeuro
Roger L Albin, Christine Minderovic, Robert A Koeppe
Considerable prior work suggests basal ganglia dysfunction in Tourette syndrome (TS). Analysis of a small number of postmortem specimens suggests deficits of some striatal interneuron populations, including striatal cholinergic interneurons. To assess the integrity of striatal cholinergic interneurons in TS, we used [(18)F]FEOBV positron emission tomography (PET) to quantify striatal vesicular acetylcholine transporter (VAChT) expression, a measure of cholinergic terminal density, in human TS and control subjects...
July 2017: ENeuro
Katie A Ferguson, Alexandra P Chatzikalymniou, Frances K Skinner
Scientists have observed local field potential theta rhythms (3-12 Hz) in the hippocampus for decades, but understanding the mechanisms underlying their generation is complicated by their diversity in pharmacological and frequency profiles. In addition, interactions with other brain structures and oscillatory drives to the hippocampus during distinct brain states has made it difficult to identify hippocampus-specific properties directly involved in theta generation. To overcome this, we develop cellular-based network models using a whole hippocampus in vitro preparation that spontaneously generates theta rhythms...
July 2017: ENeuro
Wendy K Adams, Cole Vonder Haar, Melanie Tremblay, Paul J Cocker, Mason M Silveira, Sukhbir Kaur, Christelle Baunez, Catharine A Winstanley
Deep brain stimulation of the subthalamic nucleus (STN-DBS) can improve the motor symptoms of Parkinson's disease (PD) and negate the problematic side effects of dopamine replacement therapy. Although there is concern that STN-DBS may enhance the development of gambling disorder and other impulse control disorders in this patient group, recent data suggest that STN-DBS may actually reduce iatrogenic impulse control disorders, and alleviate obsessive-compulsive disorder (OCD). Here, we sought to determine whether STN-DBS was beneficial or detrimental to performance of the rat gambling task (rGT), a rodent analogue of the Iowa Gambling Task (IGT) used to assess risky decision making clinically...
July 2017: ENeuro
Ida E J Aasebø, Mikkel E Lepperød, Maria Stavrinou, Sandra Nøkkevangen, Gaute Einevoll, Torkel Hafting, Marianne Fyhn
The activity pattern and temporal dynamics within and between neuron ensembles are essential features of information processing and believed to be profoundly affected by anesthesia. Much of our general understanding of sensory information processing, including computational models aimed at mathematically simulating sensory information processing, rely on parameters derived from recordings conducted on animals under anesthesia. Due to the high variety of neuronal subtypes in the brain, population-based estimates of the impact of anesthesia may conceal unit- or ensemble-specific effects of the transition between states...
July 2017: ENeuro
Robson Scheffer-Teixeira, Adriano B L Tort
Phase-amplitude coupling analysis shows that theta phase modulates oscillatory activity not only within the traditional gamma band (30-100 Hz) but also at faster frequencies, called high-frequency oscillations (HFOs; 120-160 Hz). To date, however, theta-associated HFOs have been reported by only a small number of laboratories. Here we characterized coupling patterns during active waking (aWk) and rapid eye movement (REM) sleep in local field potentials (LFPs) from the parietal cortex and hippocampus of rats, focusing on how theta-associated HFOs can be detected...
July 2017: ENeuro
Bernhard Spitzer, Saskia Haegens
Among the rhythms of the brain, oscillations in the beta frequency range (∼13-30 Hz) have been considered the most enigmatic. Traditionally associated with sensorimotor functions, beta oscillations have recently become more broadly implicated in top-down processing, long-range communication, and preservation of the current brain state. Here, we extend and refine these views based on accumulating new findings of content-specific beta-synchronization during endogenous information processing in working memory (WM) and decision making...
July 2017: ENeuro
Yihe Ma, Peter O Bayguinov, Meyer B Jackson
The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus...
July 2017: ENeuro
Monique L Smith, Andre T Walcott, Mary M Heinricher, Andrey E Ryabinin
Pain is often described as a "biopsychosocial" process, yet social influences on pain and underlying neural mechanisms are only now receiving significant experimental attention. Expression of pain by one individual can be communicated to nearby individuals by auditory, visual, and olfactory cues. Conversely, the perception of another's pain can lead to physiological and behavioral changes in the observer, which can include induction of hyperalgesia in "bystanders" exposed to "primary" conspecifics in which hyperalgesia has been induced directly...
July 2017: ENeuro
Jay Spampanato, F Edward Dudek
The death of GABAergic interneurons has long been hypothesized to contribute to acquired epilepsy. These experiments tested the hypothesis that focal interneuron lesions cause acute seizures [i.e., status epilepticus (SE)] and/or chronic epilepsy [i.e., persistent spontaneous recurrent seizures (SRSs)]. To selectively ablate interneurons, Gad2-ires-Cre mice were injected unilaterally in the CA1 area of the dorsal hippocampus with an adeno-associated virus containing the diphtheria toxin receptor (DTR). Simultaneously, an electrode, connected to a miniature telemetry device, was positioned at the injection site for chronic recordings of local field potentials (LFPs)...
July 2017: ENeuro
Perrine Friedel, Anastasia Ludwig, Christophe Pellegrino, Morgane Agez, Anass Jawhari, Claudio Rivera, Igor Medina
A plethora of neurological disorders are associated with alterations in the expression and localization of potassium-chloride cotransporter type 2 (KCC2), making KCC2 a critical player in neuronal function and an attractive target for therapeutic treatment. The activity of KCC2 is determined primarily by the rates of its surface insertion and internalization. Currently the domains of KCC2 dictating its trafficking and endocytosis are unknown. Here, using live-cell immunolabeling and biotinylation of KCC2 proteins expressed in murine neuroblastoma N2a cells, human embryonic kidney 293 cells, or primary cultures of rat hippocampal neurons, we identified a novel role for the intracellular N and C termini in differentially regulating KCC2 surface expression...
July 2017: ENeuro
Andrew Kneynsberg, Nicholas M Kanaan
Little is known about the specific contributions of aging to the neuron dysfunction and death in Alzheimer's disease (AD). AD is characterized by the pathological accumulation of abnormal tau (a microtubule-associated protein), and the mislocalization of tau from the axon to the somatodendritic compartment is thought to play an important role in disease pathogenesis. The axon initial segment (AIS) is thought to play a role in the selective localization of tau in the axonal compartment. Thus, disruption in the AIS barrier may allow tau to diffuse freely back into the somatodendritic compartment and potentially lead to neurotoxicity...
July 2017: ENeuro
Denise Isabelle Briggs, Erwin Defensor, Pooneh Memar Ardestani, Bitna Yi, Michelle Halpain, Guy Seabrook, Mehrdad Shamloo
Emerging evidence suggests that endoplasmic reticulum (ER) stress may be involved in the pathogenesis of Alzheimer's disease (AD). Recently, pharmacological modulation of the eukaryotic translation initiation factor-2 (eIF2α) pathway was achieved using an integrated stress response inhibitor (ISRIB). While members of this signaling cascade have been suggested as potential therapeutic targets for neurodegeneration, the biological significance of this pathway has not been comprehensively assessed in animal models of AD...
July 2017: ENeuro
Baiping Wang, Hongmei Li, Sena A Mutlu, Devon A Bowser, Michael J Moore, Meng C Wang, Hui Zheng
The amyloid precursor protein (APP) is a receptor-like membrane protein. Although APP processing and β-amyloid production play a central role in Alzheimer's disease (AD) pathogenesis, the physiological function of APP remains elusive. Here, we identify APP as a novel receptor for Slit that mediates axon guidance and neural circuit formation. APP deficiency abolishes the Slit repulsive effect in a 3D olfactory explant culture, consistent with its callosal projection deficit in vivo and reminiscent of Slit loss...
May 2017: ENeuro
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