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interneurons epilepsy

Chen Qiu, Zhouyan Feng, Lvpiao Zheng, Lu Huang
Deep brain stimulation (DBS) has a good prospect in treating brain diseases such as epilepsy. However, its therapeutic mechanism is undetermined yet. To investigate the inhibitory effects of DBS acting on the downstream neurons in target region, 1-min pulse trains of orthodromic stimulations with various frequencies (10 - 100 Hz) were applied to the Schaffer collaterals of hippocampal CA1 region in anaesthetized rats. Unit spikes of downstream interneurons and pyramidal cells were detected and analyzed. Interneurons activated by the stimulation through mono-synaptic connections were recognized based on short latencies...
July 2018: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Firas H Farah, Vasily Grigorovsky, Berj L Bardakjian
Glial populations within neuronal networks of the brain have recently gained much interest in the context of hyperexcitability and epilepsy. In this paper, we present an oscillator-based neuroglial model capable of generating Spontaneous Electrical Discharges (SEDs) in hyperexcitable conditions. The network is composed of 16 coupled Cognitive Rhythm Generators (CRGs), which are oscillator-based mathematical constructs previously described by our research team. CRGs are well-suited for modeling assemblies of excitable cells, and in this network, each represents one of the following populations: excitatory pyramidal cells, inhibitory interneurons, astrocytes, and microglia...
September 16, 2018: International Journal of Neural Systems
Yo-Tsen Liu, Yi-Chieh Chen, Shang-Yeong Kwan, Chien-Chen Chou, Hsiang-Yu Yu, Der-Jen Yen, Kwong-Kum Liao, Wei-Ta Chen, Yung-Yang Lin, Rou-Shayn Chen, Kang-Yang Jih, Shu-Fen Lu, Yu-Te Wu, Po-Shan Wang, Fu-Jung Hsiao
Paroxysmal kinesigenic dyskinesia (PKD) is conventionally regarded as a movement disorder (MD) and characterized by episodic hyperkinesia by sudden movements. However, patients of PKD often have sensory aura and respond excellently to antiepileptic agents. PRRT2 mutations, the most common genetic etiology of PKD, could cause epilepsy syndromes as well. Standing in the twilight zone between MDs and epilepsy, the pathogenesis of PKD is unclear. Gamma oscillations arise from the inhibitory interneurons which are crucial in the thalamocortical circuits...
2018: Frontiers in Neurology
Txomin Lalanne, Julia Oyrer, Mark Farrant, P Jesper Sjöström
Calcium-permeable (CP) AMPA-type glutamate receptors (AMPARs) are known to mediate synaptic plasticity in several different interneuron (IN) types. Recent evidence suggests that CP-AMPARs are synapse-specifically expressed at excitatory connections onto a subset of IN types in hippocampus and neocortex. For example, CP-AMPARs are found at connections from pyramidal cells (PCs) to basket cells (BCs), but not to Martinotti cells (MCs). This synapse type-specific expression of CP-AMPARs suggests that synaptic dynamics as well as learning rules are differentially implemented in local circuits and has important implications not just in health but also in disease states such as epilepsy...
2018: Frontiers in Synaptic Neuroscience
Nickesha C Anderson, Meghan A Van Zandt, Swechhya Shrestha, Daniel B Lawrence, Jyoti Gupta, Christopher Y Chen, Felicia A Harrsch, Trinithas Boyi, Carolyn E Dundes, Gloster Aaron, Janice R Naegele, Laura Grabel
GABAergic interneuron dysfunction has been implicated in temporal lobe epilepsy (TLE), autism, and schizophrenia. Inhibitory interneuron progenitors transplanted into the hippocampus of rodents with TLE provide varying degrees of seizure suppression. We investigated whether human embryonic stem cell (hESC)-derived interneuron progenitors (hESNPs) could differentiate, correct hippocampal-dependent spatial memory deficits, and suppress seizures in a pilocarpine-induced TLE mouse model. We found that transplanted ventralized hESNPs differentiated into mature GABAergic interneurons and became electrophysiologically active with mature firing patterns...
October 5, 2018: Stem Cell Research
Vincent Magloire, Marion S Mercier, Dimitri M Kullmann, Ivan Pavlov
Seizures are complex pathological network events characterized by excessive and hypersynchronized activity of neurons, including a highly diverse population of GABAergic interneurons. Although the primary function of inhibitory interneurons under normal conditions is to restrain excitation in the brain, this system appears to fail intermittently, allowing runaway excitation. Recent developments in optogenetics, combined with genetic tools and advanced electrophysiological and imaging techniques, allow us for the first time to assess the causal roles of identified cell-types in network dynamics...
October 15, 2018: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
Adam Gorlewicz, Leszek Kaczmarek
Chemical synapses are specialized interfaces between neurons in the brain that transmit and modulate information, thereby integrating cells into multiplicity of interacting neural circuits. Cell adhesion molecules (CAMs) might form trans-synaptic complexes that are crucial for the appropriate identification of synaptic partners and further for the establishment, properties, and dynamics of synapses. When affected, trans-synaptic adhesion mechanisms play a role in synaptopathies in a variety of neuropsychiatric disorders including epilepsy...
2018: Frontiers in Cell and Developmental Biology
Tabish Hussain, Hyunsuk Kil, Bharathi Hattiangady, Jaeho Lee, Maheedhar Kodali, Bing Shuai, Sahithi Attaluri, Yoko Takata, Jianjun Shen, Martin C Abba, Ashok K Shetty, C Marcelo Aldaz
The association of WW domain-containing oxidoreductase WWOX gene loss of function with central nervous system (CNS) related pathologies is well documented. These include spinocerebellar ataxia, epilepsy and mental retardation (SCAR12, OMIM: 614322) and early infantile epileptic encephalopathy (EIEE28, OMIM: 616211) syndromes. However, there is complete lack of understanding of the pathophysiological mechanisms at play. In this study, using a Wwox knockout (Wwox KO) mouse model (2 weeks old, both sexes) and stereological studies we observe that Wwox deletion leads to a significant reduction in the number of hippocampal GABA-ergic (γ-aminobutyric acid) interneurons...
October 2, 2018: Neurobiology of Disease
Alexandru Cǎlin, Mihai Stancu, Ana-Maria Zagrean, John G R Jefferys, Andrei S Ilie, Colin J Akerman
Current anti-epileptic medications that boost synaptic inhibition are effective in reducing several types of epileptic seizure activity. Nevertheless, these drugs can generate significant side-effects and even paradoxical responses due to the broad nature of their action. Recently developed chemogenetic techniques provide the opportunity to pharmacologically recruit endogenous inhibitory mechanisms in a selective and circuit-specific manner. Here, we use chemogenetics to assess the potential of suppressing epileptiform activity by enhancing the synaptic output from three major interneuron populations in the rodent hippocampus: parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) expressing interneurons...
2018: Frontiers in Cellular Neuroscience
Qiyu Zhu, Wei Ke, Quansheng He, Xiongfei Wang, Rui Zheng, Tianfu Li, Guoming Luan, Yue-Sheng Long, Wei-Ping Liao, Yousheng Shu
Inhibitory GABAergic interneurons are fundamental elements of cortical circuits and play critical roles in shaping network activity. Dysfunction of interneurons can lead to various brain disorders, including epilepsy, schizophrenia, and anxiety. Based on the electrophysiological properties, cell morphology, and molecular identity, interneurons could be classified into various subgroups. In this study, we investigated the density and laminar distribution of different interneuron types and the co-expression of molecular markers in epileptic human cortex...
August 31, 2018: Neuroscience Bulletin
Linda K Friedman, Joann P Wongvravit
Anticonvulsant effects of cannabidiol (CBD), a nonpsychoactive cannabinoid, have not been investigated in the juvenile brain. We hypothesized that CBD would attenuate epileptiform activity at an age when the brain first becomes vulnerable to neurotoxicity and social/cognitive impairments. To induce seizures, kainic acid (KA) was injected either into the hippocampus (KAih) or systemically (KAip) on postnatal (P) day 20. CBD was coadministered (KA + CBDih, KA + CBDip) or injected 30 minutes postseizure onset (KA/CBDih, KA/CBDip)...
October 1, 2018: Journal of Neuropathology and Experimental Neurology
Bao-Liang Zhang, Yue-Shan Fan, Ji-Wei Wang, Zi-Wei Zhou, Yin-Gang Wu, Meng-Chen Yang, Dong-Dong Sun, Jian-Ning Zhang
Traumatic brain injury can cause loss of neuronal tissue, remote symptomatic epilepsy, and cognitive deficits. However, the mechanisms underlying the effects of traumatic brain injury are not yet clear. Hippocampal excitability is strongly correlated with cognitive dysfunction and remote symptomatic epilepsy. In this study, we examined the relationship between traumatic brain injury-induced neuronal loss and subsequent hippocampal regional excitability. We used hydraulic percussion to generate a rat model of traumatic brain injury...
October 2018: Neural Regeneration Research
William A Catterall
Dravet Syndrome is a devastating childhood epilepsy disorder with high incidence of premature death plus comorbidities of ataxia, circadian rhythm disorder, impaired sleep quality, autistic-like social-interaction deficits and severe cognitive impairment. It is primarily caused by heterozygous loss-of-function mutations in the SCN1A gene that encodes brain voltage-gated sodium channel type-1, termed NaV 1.1. Here I review experiments on mouse genetic models that implicate specific loss of sodium currents and action potential firing in GABAergic inhibitory interneurons as the fundamental cause of Dravet Syndrome...
April 2018: Current Opinion in Physiology
Morgana Favero, Nathaniel P Sotuyo, Emily Lopez, Jennifer A Kearney, Ethan M Goldberg
Dravet syndrome is a severe, childhood-onset epilepsy largely due to heterozygous loss-of-function mutation of the gene SCN1A , which encodes the type 1 neuronal voltage-gated sodium (Na+ ) channel α subunit Nav1.1. Prior studies in mouse models of Dravet syndrome ( Scn1a +/- mice) indicate that, in cerebral cortex, Nav1.1 is predominantly expressed in GABAergic interneurons, in particular in parvalbumin-positive fast-spiking basket cell interneurons (PVINs). This has led to a model of Dravet syndrome pathogenesis in which Nav1...
September 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Kay L Richards, Carol J Milligan, Robert J Richardson, Nikola Jancovski, Morten Grunnet, Laura H Jacobson, Eivind A B Undheim, Mehdi Mobli, Chun Yuen Chow, Volker Herzig, Agota Csoti, Gyorgy Panyi, Christopher A Reid, Glenn F King, Steven Petrou
Dravet syndrome is a catastrophic, pharmacoresistant epileptic encephalopathy. Disease onset occurs in the first year of life, followed by developmental delay with cognitive and behavioral dysfunction and substantially elevated risk of premature death. The majority of affected individuals harbor a loss-of-function mutation in one allele of SCN1A , which encodes the voltage-gated sodium channel NaV 1.1. Brain NaV 1.1 is primarily localized to fast-spiking inhibitory interneurons; thus the mechanism of epileptogenesis in Dravet syndrome is hypothesized to be reduced inhibitory neurotransmission leading to brain hyperexcitability...
August 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
Xiao Jiang, Alexis Lupien-Meilleur, Sabrina Tazerart, Mathieu Lachance, Elena Samarova, Roberto Araya, Jean-Claude Lacaille, Elsa Rossignol
OBJECTIVE: Deletions of CACNA1A, encoding the α1 subunit of CaV 2.1 channels, cause epilepsy with ataxia in humans. Whereas the deletion of Cacna1a in γ-aminobutyric acidergic (GABAergic) interneurons (INs) derived from the medial ganglionic eminence (MGE) impairs cortical inhibition and causes generalized seizures in Nkx2.1Cre ;Cacna1ac/c mice, the targeted deletion of Cacna1a in somatostatin-expressing INs (SOM-INs), a subset of MGE-derived INs, does not result in seizures, indicating a crucial role of parvalbumin-expressing (PV) INs...
September 2018: Annals of Neurology
Hannah Hayhurst, Maria-Eleni Anagnostou, Helen J Bogle, John P Grady, Robert W Taylor, Laurence A Bindoff, Robert McFarland, Doug M Turnbull, Nichola Z Lax
Alpers' syndrome is an early-onset neurodegenerative disorder often caused by biallelic pathogenic variants in the gene encoding the catalytic subunit of polymerase-gamma (POLG) which is essential for mitochondrial DNA (mtDNA) replication. Alpers' syndrome is characterized by intractable epilepsy, developmental regression and liver failure which typically affects children aged 6 months-3 years. Although later onset variants are now recognized, they differ in that they are primarily an epileptic encephalopathy with ataxia...
July 18, 2018: Brain Pathology
Rigil K Yeung, Zheng-Hua Xiang, Shui-Ying Tsang, Rui Li, Timothy Y C Ho, Qi Li, Chok-King Hui, Pak-Chung Sham, Ming-Qi Qiao, Hong Xue
Intronic polymorphisms of the GABAA receptor β2 subunit gene (GABRB2) under adaptive evolution were associated with schizophrenia and reduced expression, especially of the long isoform which differs in electrophysiological properties from the short isoform. The present study was directed to examining the gene dosage effects of Gabrb2 in knockout mice of both heterozygous (HT) and homozygous (KO) genotypes with respect to possible schizophrenia-like and comorbid phenotypes. The KO mice, and HT mice to a lesser extent, were found to display prepulse inhibition (PPI) deficit, locomotor hyperactivity, stereotypy, sociability impairments, spatial-working and spatial-reference memory deficits, reduced depression and anxiety, and accelerated pentylenetetrazol (PTZ)-induced seizure...
July 17, 2018: Translational Psychiatry
Qian Zhu, Janice R Naegele, Sangmi Chung
Epilepsy is a severe neurological disease affecting more than 70 million people worldwide that is characterized by unpredictable and abnormal electrical discharges resulting in recurrent seizures. Although antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment for seizure control, about one third of patients with epilepsy suffer from intractable seizures that are unresponsive to AEDs. Furthermore, the patients that respond to AEDs typically experience adverse systemic side effects, underscoring the urgent need to develop new therapies that target epileptic foci rather than more systemic interventions...
2018: Frontiers in Cellular Neuroscience
Rafael Falcón-Moya, Talvinder S Sihra, Antonio Rodríguez-Moreno
Kainate (KA) is a potent neurotoxin that has been widely used experimentally to induce acute brain seizures and, after repetitive treatments, as a chronic model of temporal lobe epilepsy (TLE), with similar features to those observed in human patients with TLE. However, whether KA activates KA receptors (KARs) as an agonist to mediate the induction of acute seizures and/or the chronic phase of epilepsy, or whether epileptogenic effects of the neurotoxin are indirect and/or mediated by other types of receptors, has yet to be satisfactorily elucidated...
2018: Frontiers in Molecular Neuroscience
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