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interneurons epilepsy

Ann M Clemens, Constanze Lenschow, Prateep Beed, Lanxiang Li, Rosanna Sammons, Robert K Naumann, Hong Wang, Dietmar Schmitz, Michael Brecht
Female mammals experience cyclical changes in sexual receptivity known as the estrus cycle. Little is known about how estrus affects the cortex, although alterations in sensation, cognition and the cyclical occurrence of epilepsy suggest brain-wide processing changes. We performed in vivo juxtacellular and whole-cell recordings in somatosensory cortex of female rats and found that the estrus cycle potently altered cortical inhibition. Fast-spiking interneurons were strongly activated with social facial touch and varied their ongoing activity with the estrus cycle and estradiol in ovariectomized females, while regular-spiking excitatory neurons did not change...
February 5, 2019: Current Biology: CB
Jian-Ping Zhao, Akira Yoshii
Tuberous sclerosis complex (TSC) is a neurogenetic disorder associated with epilepsy, intellectual disabilities, and autistic behaviors. These neurological symptoms result from synaptic dysregulations, which shift a balance between excitation and inhibition. To decipher the synaptic substrate of hyperexcitability, we examined pan-neuronal Tsc1 knockout mouse and found a reduction in surface expression of a GABA receptor (GABAR) subunit but not AMPA receptor (AMPAR) subunit. Using electrophysiological recordings, we found a significant reduction in the frequency of GABAR-mediated miniature inhibitory postsynaptic currents (GABAR-mIPSCs) but not AMPAR-mediated miniature excitatory postsynaptic currents (AMPAR-mEPSCs) in layer 2/3 pyramidal neurons...
January 25, 2019: Molecular Brain
Giovanna Paolone, Chiara Falcicchia, Francesca Lovisari, Merab Kokaia, William J Bell, Tracie Fradet, Mario Barbieri, Lars U Wahlberg, Dwaine F Emerich, Michele Simonato
Neurotrophic factors are candidates for treating epilepsy but their development has been hampered by difficulties in achieving stable and targeted delivery of efficacious concentrations within the desired brain region. We have developed an encapsulated cell technology that overcomes these obstacles by providing a targeted, continuous, de novo synthesized source of high levels of neurotrophic molecules from human clonal ARPE-19 cells encapsulated into hollow fiber membranes. Here we illustrate the potential of this approach for delivering glial cell line-derived neurotrophic factor (GDNF) directly to the hippocampus of epileptic rats...
January 21, 2019: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Zoe Noakes, Francesca Keefe, Claudia Tamburini, Claire M Kelly, Maria Cruz Santos, Stephen B Dunnett, Adam C Errington, Meng Li
Striatal interneurons are born in the medial and caudal ganglionic eminences (MGE and CGE) and play an important role in human striatal function and dysfunction in Huntington's disease and dystonia. MGE/CGE-like neural progenitors have been generated from human pluripotent stem cells (hPSCs) for studying cortical interneuron development and cell therapy for epilepsy and other neurodevelopmental disorders. Here, we report the capacity of hPSC-derived MGE/CGE-like progenitors to differentiate into functional striatal interneurons...
February 12, 2019: Stem Cell Reports
Zhu Li, Rekha Jagadapillai, Evelyne Gozal, Gregory Barnes
Autism and epilepsy are diseases which have complex genetic inheritance. Genome-wide association and other genetic studies have implicated at least 500+ genes associated with the occurrence of autism spectrum disorders (ASD) including the human semaphorin 3F (Sema 3F) and neuropilin 2 (NRP2) genes. However, the genetic basis of the comorbid occurrence of autism and epilepsy is unknown. The aberrant development of GABAergic circuitry is a possible risk factor in autism and epilepsy. Molecular biological approaches were used to test the hypothesis that cell-specific genetic variation in mouse homologs affects the formation and function of GABAergic circuitry...
January 11, 2019: Molecular Neurobiology
Thomas Blauwblomme, Elena Dossi, Christophe Pellegrino, Emmanuelle Goubert, Beatriz Gal Iglesias, Christian Sainte-Rose, Nathalie Rouach, Rima Nabbout, Gilles Huberfeld
OBJECTIVE: Dysregulation of GABAergic transmission has been reported in lesional acquired epilepsies (gliomas, hippocampal sclerosis). We investigated its involvement in a developmental disorder, human Focal Cortical Dysplasia, focusing on chloride regulation driving GABAergic signals. METHODS: In vitro recordings of 47 human cortical acute slices from 11 pediatric patients operated from a Focal Cortical Dysplasia were performed on Multi Electrode Arrays. GABAergic receptors and chloride regulators were pharmacologically modulated...
December 31, 2018: Annals of Neurology
Nadia Kafui Adotevi, Beulah Leitch
Childhood absence epilepsy has been associated with poor academic performance, behavioural difficulties, as well as increased risk of physical injury in some affected children. The frequent episodes of 'absence' arise from corticothalamocortical network dysfunction, with multifactorial mechanisms potentially involved in genetically different patients. Aberrations in glutamatergic neurotransmission has been implicated in some seizure models, and we have recently reported that reduced cortical AMPA receptor (AMPAR) expression (predominantly GluA4- containing AMPARs) in parvalbumin-containing (PV+ ) inhibitory interneurons, could underlie seizure generation in the stargazer mutant mouse...
December 26, 2018: International Journal of Developmental Neuroscience
Mustafa Q Hameed, Tsung-Hsun Hsieh, Leon Morales-Quezada, Henry H C Lee, Ugur Damar, Paul C MacMullin, Takao K Hensch, Alexander Rotenberg
Traumatic brain injury (TBI) results in a decrease in glutamate transporter-1 (GLT-1) expression, the major mechanism for glutamate removal from synapses. Coupled with an increase in glutamate release from dead and dying neurons, this causes an increase in extracellular glutamate. The ensuing glutamate excitotoxicity disproportionately damages vulnerable GABAergic parvalbumin-positive inhibitory interneurons, resulting in a progressively worsening cortical excitatory:inhibitory imbalance due to a loss of GABAergic inhibitory tone, as evidenced by chronic post-traumatic symptoms such as epilepsy, and supported by neuropathologic findings...
December 22, 2018: Cerebral Cortex
Anna-Maria Katsarou, Qianyun Li, Wei Liu, Solomon L Moshé, Aristea S Galanopoulou
West syndrome, an age-specific epileptic encephalopathy, manifests with infantile spasms (IS) and impaired neurodevelopmental outcomes and epilepsy. The multiple-hit rat model of IS is a chronic model of IS due to structural etiology, in which spasms respond partially to vigabatrin analogs. Using this model, we investigated whether IS due to structural etiology may have deficits in parvalbumin (PRV) and somatostatin (SST) immunoreactive (-ir) interneurons, and calretinin-ir (CR-ir) neurons of the primary somatosensory cortex of postnatal day (PN) 20-24 rats, using specific immunohistochemical assays...
December 2018: Epilepsia Open
Anton V Chizhov, Dmitry V Amakhin, Aleksey V Zaitsev
Interictal discharges (IIDs) accompany epileptic seizures and highlight the mechanisms of pathological activity. The propagation of IIDs along the neural tissue is not well understood. To simulate IID propagation, this study proposes a new mathematical model that uses the conductance-based refractory density approach for glutamatergic and GABAergic neuronal populations. The mathematical model is found to be consistent with experimental double-patch registrations in the 4-aminopyridine in vitro model of epilepsy...
December 15, 2018: Biochemical and Biophysical Research Communications
Dinesh Upadhya, Bharathi Hattiangady, Olagide W Castro, Bing Shuai, Maheedhar Kodali, Sahithi Attaluri, Adrian Bates, Yi Dong, Su-Chun Zhang, Darwin J Prockop, Ashok K Shetty
Medial ganglionic eminence (MGE)-like interneuron precursors derived from human induced pluripotent stem cells (hiPSCs) are ideal for developing patient-specific cell therapy in temporal lobe epilepsy (TLE). However, their efficacy for alleviating spontaneous recurrent seizures (SRS) or cognitive, memory, and mood impairments has never been tested in models of TLE. Through comprehensive video- electroencephalographic recordings and a battery of behavioral tests in a rat model, we demonstrate that grafting of hiPSC-derived MGE-like interneuron precursors into the hippocampus after status epilepticus (SE) greatly restrained SRS and alleviated cognitive, memory, and mood dysfunction in the chronic phase of TLE...
January 2, 2019: Proceedings of the National Academy of Sciences of the United States of America
Noa Sadigurschi, Hava M Golan
Individuals with autism constitute a variable population whose members are spread along the autism spectrum. Subpopulations within that spectrum exhibit other conditions, such as anxiety, intellectual disabilities, hyperactivity and epilepsy, with different severities and co-occurrences. Among the genes associated with the increased risk for autism is the methylenetetrahydrofolate-reductase (MTHFR) 677C>T polymorphism, which impairs one-carbon (C1) metabolic pathway efficiency. The frequency of the MTHFR677TT homozygote is markedly higher among autism patients and their mothers than in the general population...
January 2019: Genes, Brain, and Behavior
Florian Studer, Emel Laghouati, Guillaume Jarre, Olivier David, Benoît Pouyatos, Antoine Depaulis
KEY POINTS: Absence epilepsy is characterized by the occurrence of spike-and-wave discharges concomitant with an alteration of consciousness and associated with cognitive comorbidities. In a genetic model of absence epilepsy in the rat, the GAERS, we showed that spike-and-wave discharges are initiated in the barrel field primary somatosensory cortex that codes whisker-related information therefore playing an essential role in rodents' interactions with their environment. Sensory-information processing is impaired in the epileptic barrel field primary somatosensory cortex of GAERS with a delayed sensory-evoked potential and a duplicated neuronal response to whisker-stimulation in in vivo extracellular recordings...
December 13, 2018: Journal of Physiology
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
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