A5016901102- Neuroscience and Neuropharmacology Research
- Epilepsy research and treatment
- Ion channel regulation and function
- Hearing, Cochlea, Tinnitus, Genetics
- Genetics and Neurodevelopmental Disorders
- Receptor Mechanisms and Signaling
- Hearing Loss and Rehabilitation
- Noise Effects and Management
- Cardiac electrophysiology and arrhythmias
- Vestibular and auditory disorders
- Neonatal and fetal brain pathology
- Mitochondrial Function and Pathology
- Genomics and Rare Diseases
- Speech and Audio Processing
- Ear Surgery and Otitis Media
- Pancreatic function and diabetes
- Photoreceptor and optogenetics research
- Diet and metabolism studies
- Schizophrenia research and treatment
- Birth, Development, and Health
- Ion Channels and Receptors
- Ultrasonics and Acoustic Wave Propagation
- Respiratory Support and Mechanisms
- Cancer-related molecular mechanisms research
- Memory and Neural Mechanisms
Tel Aviv University
2014-2025
Smith-Kettlewell Eye Research Institute
2023-2025
Sheba Medical Center
1975-2021
University of Washington
2014-2016
Edmond and Lily Safra Children's Hospital
2007
University of Michigan
1990
The University of Texas Health Science Center at Houston
1980
A modified quadripolar electrode catheter that had two-thirds of the distal surface insulated with high-voltage plastic was inserted in 10 dogs. After a His bundle potential been recorded, synchronized direct-current electrical discharge delivered between electrodes showing largest deflection using standard defibrillator, and metallic plate positioned over dog's back. Complete atrioventricular (AV) block induced 9 dogs, which were followed for 3 mo before being killed. During AV block, QRS...
Neurological and psychiatric syndromes often have multiple disease traits, yet it is unknown how such multi-faceted deficits arise from single mutations. Haploinsufficiency of the voltage-gated sodium channel Nav1.1 causes Dravet syndrome, an intractable childhood-onset epilepsy with hyperactivity, cognitive deficit, autistic-like behaviours, premature death. Deletion channels selectively impairs excitability GABAergic interneurons. We studied mice having selective deletion in parvalbumin-...
Maintaining average activity within a set-point range constitutes fundamental property of central neural circuits. However, whether and how set points are regulated remains unknown. Integrating genome-scale metabolic modeling experimental study neuronal homeostasis, we identified mitochondrial dihydroorotate dehydrogenase (DHODH) as regulator in hippocampal networks. The DHODH inhibitor teriflunomide stably suppressed mean firing rates via synaptic intrinsic excitability mechanisms by modulating Ca
A total of 2250 subjects from psychiatric and geriatric settings was examined for abnormal involuntary movements by the same team trained raters employing a standard examination technique rating scale. "Spontaneous" dyskinesia rates were 1.3% among 400 healthy elderly people surveyed at senior citizens centers, 4.8% medical inpatients ranged 0 to 2% patients never exposed neuroleptics. For samples neuroleptic-treated patients, prevalence 13.3% voluntary hospital 36.1% state patients....
Dravet syndrome (DS), an intractable childhood epileptic encephalopathy with a high fatality rate, is typically caused by loss-of-function mutations in one allele of SCN1A, which encodes NaV1.1, 250-kDa voltage-gated sodium channel. In contrast to other epilepsies, pharmaceutical treatment for DS limited. Here, we demonstrate that viral vector-mediated delivery codon-modified SCN1A open reading frame into the brain improves comorbidities juvenile and adolescent mice (Scn1aA1783V/WT)....
Dravet syndrome is a genetic encephalopathy characterized by severe epilepsy combined with motor, cognitive, and behavioral abnormalities. Current antiepileptic drugs achieve only partial control of seizures provide little benefit on the patient's neurological development. In >80% cases, disease caused haploinsufficiency SCN1A gene, which encodes alpha subunit Nav1.1 voltage-gated sodium channel. Novel therapies aim to restore expression in order address all manifestations. We evidence that...
Mutations in the SCN8A gene, encoding voltage-gated sodium channel Na
Dravet syndrome (Dravet) is a rare, severe childhood-onset epilepsy, caused by heterozygous de novo mutations in the SCN1A gene, encoding for alpha subunit of voltage-gated sodium channel, NaV1.1. The neuronal basis debated, with evidence favoring reduced function inhibitory neurons, that might be transient, or enhanced activity excitatory cells. Here, we utilized mice to trace developmental changes hippocampal CA1 circuit, examining properties horizontal stratum-oriens (SO) interneurons and...
Heterozygous loss of function mutations in the CHD2 gene, encoding for chromodomain helicase DNA-binding protein 2, are associated with severe childhood-onset epilepsy, global developmental delay, and autistic features. Here, we characterized behavioral epileptic phenotypes a mouse model harboring frameshift truncating mutation Chd2 gene (Chd2WT/m Chd2m/m mice). Genetic background dramatically affected phenotypes. While no were observed on pure C57BL/6J background, crossing these mice onto...
Abstract Gain-of-function (GoF) variants in the GRIN2D gene, encoding GluN2D subunit of N-methyl-D-aspartate receptor (NMDAR), cause a severe developmental and epileptic encephalopathy (DEE), characterized by intractable seizures, hypotonia, neurodevelopmental delay. We generated mice carrying GoF V664I variant, orthologous to V667I, which is present ∼25% GRIN2D-DEE patients. Heterozygous mutant demonstrate behavioral, neuroanatomical, electrophysiological abnormalities. Lethal convulsive...
Abstract Pathogenic variants in GRIN2D, encoding one of the subunits NMDA receptor (NMDAR), are associated with developmental and epileptic encephalopathies (DEEs). Unusual for de novo mutations, recurrent, de-novo, gain function, missense mutation c.1999G>A (p.Val667Ile) was discovered multiple patients. We characterized a mouse model carrying orthologous Grin2d mutation, using behavioral paradigms, electrophysiological recordings acute brain slices focusing mainly on activity...
G protein activated K+ channels (GIRK, Kir3) are switched on by direct binding of Gbetagamma following activation Gi/o proteins via protein-coupled receptors (GPCRs). Although Galphai subunits do not activate GIRKs, they interact with the and regulate gating pattern neuronal heterotetrameric GIRK1/2 channel (composed GIRK1 GIRK2 subunits) expressed in Xenopus oocytes. Coexpressed Galphai3 decreases basal activity (Ibasal) increases extent purified or coexpressed Gbegagamma. Here we show that...
With the objective of studying a possible correlation between chronic cardiovascular disturbances and hearing loss in aged people, two groups were compared. The first was composed apparently healthy subjects second, suffering from clinically evident pathology. All submitted to pure tone audiometry, discrimination test, SISI test TDT. results showed significant difference threshold audiometry those presenting symptoms; TDT comparable groups.
Autism spectrum disorder (ASD) is a complex neurodevelopmental often accompanied by intellectual disability, language impairment and medical co-morbidities. The heritability of autism high multiple genes have been implicated as causal. However, most these identified in de novo cases. To further the understanding familial autism, we performed whole-exome sequencing on five families which second- third-degree relatives were affected. By focusing novel protein-altering variants, small set...
Abstract Objective Dravet syndrome (Dravet) is a severe childhood epileptic encephalopathy. The disease begins with febrile stage, characterized by seizures otherwise normal development. Progression to the worsening stage features recurrent intractable and presentation of additional nonepileptic comorbidities, including global developmental delay, hyperactivity, motor deficits. Later in life, at stabilization seizure burden decreases, whereas Dravet‐associated comorbidities persist. To date,...
The IGF system plays an important role in prostate cancer initiation and progression. Most of the biological actions IGF-I IGF-II are mediated by activation receptor (IGF-IR). Evidence accumulated recent years indicates that acquisition malignant phenotype is initially IGF-IR dependent, but progression toward metastatic stages usually associated with a decrease levels. Kruppel-like factor 6 (KLF6) zinc finger-containing transcription was shown to be mutated significant portion other types...
G protein-activated K+ channels (GIRK) mediate postsynaptic inhibitory effects of neurotransmitters in the atrium and brain by coupling to protein-coupled receptors (GPCRs). In neurotransmitter-dependent GIRK signalling, Gbetagamma is released from heterotrimeric Galphabetagamma complex upon GPCR activation, activating channel attenuating its rectification. Now it becomes clear that Galpha more than a mere donor. We have proposed Galphai3-GDP regulates gating, keeping basal activity low but...
Comparative measurements of the cochlear electrical activity over prolonged periods require long-term implantation electrodes. During this time, changes in electrode recording ability and/or impairment sound-conducting system, could erroneously be attributed to experiment. To avoid risk, an easy and reliable technique is described. The procedure uses Fallopian canal as a route by which approach potentials' generators, while leaving middle ear untouched.
Stable complexes among G proteins and effectors are an emerging concept in cell signaling. The prototypical betagamma effector protein-activated K(+) channel (GIRK; Kir3) physically interacts with but also alpha(i/o). Whether how alpha(i/o) subunits regulate GIRK vivo is unclear. We studied triple interactions 1 2, alpha(i3) betagamma. used vitro protein interaction assays intramolecular Förster resonance energy transfer (i-FRET) between fluorophores attached to N C termini of either GIRK1...
The Mössbauer effect has been applied to the measurements of phase and amplitude relations in vibrations guinea pig ear vivo induced by sound normal hearing range. Measurements were made on umbo incudostapedial joint. relative was near zero throughout measured frequency range 250 cps-9 kc/sec, lever-ratio nearly constant at a value about 2.0.