A5073764338- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Neural dynamics and brain function
- Ion channel regulation and function
- Genetic Neurodegenerative Diseases
- Vestibular and auditory disorders
- Neuroscience and Neural Engineering
- Mitochondrial Function and Pathology
- Nicotinic Acetylcholine Receptors Study
- Biochemical Analysis and Sensing Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Hearing, Cochlea, Tinnitus, Genetics
- Molecular Sensors and Ion Detection
- Memory and Neural Mechanisms
- Amino Acid Enzymes and Metabolism
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- Lipid Membrane Structure and Behavior
- Photochromic and Fluorescence Chemistry
- Neurogenesis and neuroplasticity mechanisms
- Neurology and Historical Studies
- Neurobiology and Insect Physiology Research
- RNA regulation and disease
- Cardiac electrophysiology and arrhythmias
University College London
2018-2023
Wellcome Centre for Human Neuroimaging
2018-2019
University of California, Los Angeles
2007-2018
Roche (Switzerland)
2015-2017
University of California System
2005-2017
Institute of Neurobiology
2006-2015
University of Utah
2012
Université Paris Cité
2008-2009
Centre National de la Recherche Scientifique
2008-2009
Délégation Paris 5
2009
Antisense oligonucleotides can correct disease-specific phenotypes in cultured motor neurons differentiated from iPSCs derived ALS patients with a C9ORF72 repeat expansion.
In the kindling model of temporal lobe epilepsy, several physiological indicators inhibition by gamma-aminobutyric acid (GABA) in hippocampal dentate gyrus are consistent with an augmented, rather than a diminished, inhibition. brain slices obtained from epileptic (kindled) rats, excitatory drive onto inhibitory interneurons was increased and paralleled reduction presynaptic autoinhibition GABA release. This augmented sensitive to zinc most likely after molecular reorganization GABAA...
1. Whole-cell and sharp electrode recordings from adult rat dentate gyrus GCs were performed in the 400-microns-thick hippocampal slice preparation maintained at 34 +/- 1 degrees C. Intrinsic membrane properties of granule cells (GCs) evaluated with use a switching current-clamp amplifier. 2. With whole-cell technique, average resting potential (RMP) was -85 mV when potassium gluconate solution used versus -74 measured acetate-filled microelectrodes. The voltage response to injected current...
Inhibitory postsynaptic currents mediated by spontaneous activation of GABAA receptors were studied using whole-cell voltage-clamp recordings in granule cells the adult rat (postnatal day 60+) dentate gyrus 400-μm-thick coronal half-brain slices maintained at 34–35°C. The average amplitude inhibitory remained constant during a given recording period (i.e. no rundown was noted). had an conductance between 200–400 pS, Cl− flux through receptor/channels since they reversed equilibrium potential...
Whole-cell patch-clamp recordings unveiled a substantial increase in the amplitude, but no change frequency, of miniature inhibitory postsynaptic currents (mIPSCs) dentate gyrus granule cells following chronic epilepsy induced by kindling. This novel and persistent enhancement gamma-aminobutyric acid type A (GABAA) receptor-mediated inhibition lasted for at least 48 hr its induction. Nearly doubling number activated functional GABAA receptor channels during mIPSCs without any single-channel...
1. Tight‐seal, whole‐cell voltage clamp recording techniques were used to characterize monosynaptically evoked GABAB currents in adult rat brain slices maintained at 34‐35 degrees C. Responses recorded from granule cells of the dentate gyrus following blockade 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX)‐, D‐2‐amino‐5‐phosphonovaleric acid (D‐AP5)‐ and picrotoxin‐sensitive fast synaptic transmission, so that remaining could be studied isolation. 2. Under these conditions, stimulation...
Although almost all ionotropic neurotransmitter receptors undergo desensitization, the onset and recovery of desensitization at a synapse have never been observed directly. We found changes in postsynaptic AMPA receptor sensitivity neurons chick cochlear nucleus, nucleus magnocellularis (nMAG), by photolysis caged glutamate immediately after activation single synaptic input. Additionally, was demonstrated via competition between synaptically released an exogenous nondesensitizing agonist,...
Miniature spontaneous inhibitory postsynaptic currents (sIPSCs) mediated by GABAA receptors were recorded using whole-cell patch clamp recordings in rat brain slices maintained vitro at 34 +/- 1 degree C. We have found that firing of action potentials principal neurons or GABAergic interneurons is not necessary to the generation sIPSCs since they persist presence 1-5 microM tetrodotoxin (TTX). The average frequency discrete exhibits a large cell-to-cell variability and between 5-15 Hz....
The Rbfox proteins (Rbfox1, Rbfox2, and Rbfox3) regulate the alternative splicing of many important neuronal transcripts have been implicated in a variety neurological disorders. However, their roles brain development function are not well understood, part due to redundancy activities. Here we show that, unlike Rbfox1 deletion, CNS-specific deletion Rbfox2 disrupts cerebellar development. Genome-wide analysis Rbfox2(-/-) RNA identifies numerous changes altering both for mature function. To...
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited disorder, which caused by a pathological expansion of polyglutamine (polyQ) tract in the coding region ATXN2 gene. Like other ataxias, SCA2 most overtly affects Purkinje cells (PCs) cerebellum. Using transgenic mouse model expressing full-length ATXN2(Q127)-complementary DNA under control Pcp2 promoter (a PC-specific promoter), we examined time course behavioral, morphologic, biochemical and physiological changes with...
Extrasynaptic GABA(A) receptors (eGABARs) allow ambient GABA to tonically regulate neuronal excitability and are implicated as targets for ethanol anesthetics. These thought be heteropentameric proteins made up of two α subunits-either α4 or α6-two β2 β3 subunits, one δ subunit. The analog 4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3(-ol) (THIP) has been proposed a selective ligand eGABARs. Behavioral in vitro studies suggest that eGABARs have nanomolar affinity THIP; however, all published...
Axonal sprouting of excitatory neurons is frequently observed in temporal lobe epilepsy, but the extent to which inhibitory interneurons undergo similar axonal reorganization remains unclear. The goal this study was determine whether somatostatin (SOM)-expressing stratum (s.) oriens hippocampus exhibit beyond their normal territory and innervate granule cells dentate gyrus a pilocarpine model epilepsy. To obtain selective labeling SOM-expressing s. oriens, Cre recombinase-dependent construct...
Kinetic properties of a native, neuronal glutamate transporter were studied by using rapid applications to outside-out patches excised from Purkinje neurons. Pulses activated anion currents associated with the that weakly antagonized antagonist kainate. In addition, kainate blocked resting conductance observed in absence glutamate. Transporter response concentration jumps under variety conditions used construct cyclic kinetic model transporter. The simulates both and flux through...
The role of postsynaptic, neuronal glutamate transporters in terminating signals at central excitatory synapses is not known. Stimulation a climbing fiber input to cerebellar Purkinje cells was shown generate an anionic current mediated by transporters. kinetics transporter currents were resolved pulses outside-out membrane patches from cells. Comparison synaptic expressed Xenopus oocytes suggests that postsynaptic uptake the synapse removes least 22 percent released glutamate. These arise...
The kinetic properties of the excitatory amino acid transporter EAAT2 were studied using rapid applications L-glutamate to outside-out patches excised from transfected human embryonic kidney 293 cells. In presence highly permeant anion SCN(-), pulses glutamate rapidly activated transient channel currents mediated by transporter. impermeant gluconate, smaller predicted result stoichiometric flux cotransported ions. Both and displayed similar kinetics, suggesting that gating charge movements...