A5029192399- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Memory and Neural Mechanisms
- Pancreatic function and diabetes
- Protein Kinase Regulation and GTPase Signaling
- Neurotransmitter Receptor Influence on Behavior
- Amino Acid Enzymes and Metabolism
- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- Mesenchymal stem cell research
- Photoreceptor and optogenetics research
- Lipid Membrane Structure and Behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Tryptophan and brain disorders
- Metabolism, Diabetes, and Cancer
- Neural dynamics and brain function
- Alzheimer's disease research and treatments
- Stress Responses and Cortisol
- Sleep and Wakefulness Research
- Nicotinic Acetylcholine Receptors Study
- 3D Printing in Biomedical Research
- Cell death mechanisms and regulation
- Axon Guidance and Neuronal Signaling
- Pharmacological Receptor Mechanisms and Effects
Niigata University
2017-2024
Tufts University
2009-2016
University of Leicester
2014-2015
University College London
2011
University of Pennsylvania
2007-2009
Kyushu University
2004-2007
Children's Hospital of Philadelphia
2007
Collaborative Research Group
2001
GABA A receptor-mediated inhibition depends on the maintenance of intracellular Cl − concentration ([Cl ] in ) at low levels. In neurons developing CNS, [Cl is elevated, E depolarizing, and consequently excitatory. Depolarizing GABAergic synaptic responses may be recapitulated various neuropathological conditions, including epilepsy. present study, rat hippocampal dentate granule cells were recorded using gramicidin perforated patch techniques varying times (1–60 d) after an epileptogenic...
Although metabotropic glutamate receptor 5 (mGluR5) is essential for cocaine self-administration and drug-seeking behavior, there limited knowledge of the cellular actions this in nucleus accumbens (NAc). mGluR5 has potential to regulate neurons directly, recent studies have shown importance regulating Ca(2+) signaling astrocytes and, as a consequence, Ca(2+)-dependent release excitatory transmitters from these glia. In study, we demonstrate that activation induces oscillations NAc with...
Gliotransmission, the release of molecules from astrocytes, regulates neuronal excitability and synaptic transmission in situ. Whether this process affects network activity vivo is not known. Using a combination astrocyte-specific molecular genetics, with electrophysiology pharmacology, we determined that gliotransmission modulates cortical slow oscillations, rhythm characterizing nonrapid eye movement sleep. Inhibition by expression dominant negative SNARE domain astrocytes affected...
Status epilepticus (SE) is a progressive and often lethal human disorder characterized by continuous or rapidly repeating seizures. Of major significance in the pathology of SE are deficits functional expression GABA A receptors (GABA Rs), sites fast synaptic inhibition brain. We demonstrate that selectively decreases phosphorylation Rs on serine residues 408/9 (S408/9) β3 subunit intimately associated protein kinase C isoforms. Dephosphorylation S408/9 unmasks basic patch-binding motif for...
Significance This study provides an understanding of how neurosteroids regulate the membrane expression α4 subunit-containing extrasynaptic GABA A receptor (GABA R) subtypes that mediate tonic inhibition. is significant because it defines unexpected molecular mechanism by which produce long-lasting changes in efficacy GABAergic expected to lead development pharmacological strategies can control number Rs on cell surface. These hold promise restoring inhibition diseases are associated with a...
Slow and persistent synaptic inhibition is mediated by metabotropic GABA B receptors (GABA Rs). Rs are responsible for the modulation of neurotransmitter release from presynaptic terminals hyperpolarization at postsynaptic sites. Postsynaptic predominantly found on dendritic spines, adjacent to excitatory synapses, but control their plasma membrane availability still controversial. Here, we explore role glutamate receptor activation in regulating function surface central neurons. We...
GABA A receptors are critical in controlling neuronal activity. Here, we examined the role for phospholipase C-related inactive protein type 1 (PRIP-1), which binds and inactivates phosphatase 1α (PP1α) facilitating receptor phospho-dependent regulation using PRIP-1 -/- mice. In wild-type animals, robust phosphorylation functional modulation of containing β3 subunits by cAMP-dependent kinase was evident, diminished mice exhibited enhanced PP1α activity compared with controls. Furthermore,...
Abstract Chemical transmitters released from astrocytes, termed gliotransmitters, modulate synaptic transmission and neuronal function. Using astrocyte‐specific inducible transgenic mice (dnSNARE mice), we have demonstrated that inhibiting gliotransmission leads to reduced activation of adenosine A1 receptors (A1R) impaired sleep homeostasis (Halassa et al. (2009) Neuron 61:213–219); Pascual (2005) Science 310:113–116). Additionally, N ‐methyl‐ D ‐aspartate receptor (NMDAR) currents are in...
Cognitive dysfunction is a common symptom in many neuropsychiatric disorders and directly correlates with poor patient outcomes. The majority of prolonged inhibitory signaling the brain mediated via GABA B receptors (GABA Rs), but molecular function these cognition ill defined. To explore significance Rs neuronal activity cognition, we created mice enhanced postsynaptic R by mutating serine 783 receptor R2 subunit (S783A), which decreased degradation. Enhanced reduced expression...
Fast synaptic inhibition in the brain is largely mediated by gamma-aminobutyric acid receptors (GABA(A)R). While pharmacological manipulation of GABA(A)R function therapeutic agents, such as benzodiazepines can have profound effects on neuronal excitation and behavior, endogenous mechanisms neurons use to regulate efficacy their impact behavior remains poorly understood. To address this issue, we created a knock-in mouse which tyrosine phosphorylation GABA(A)Rs gamma2 subunit,...
Brain-derived neurotrophic factor (BDNF) is a potent regulator of neuronal activity, neurogenesis, and depressive-like behaviors; however, downstream effectors by which BDNF exerts these varying actions remain to be determined. Here we reveal that induces long-lasting enhancements in the efficacy synaptic inhibition stabilizing γ2 subunit-containing GABA A receptors (GABA Rs) at cell surface, leading persistent reductions excitability. This effect dependent upon enhanced phosphorylation...
Significance Alterations in the efficacy of neuronal inhibition mediated by GABA A receptors (GABA Rs) containing β3 subunits are continually implicated autism spectrum disorders (ASDs). In vitro, plasma membrane stability Rs is potentiated via phosphorylation serine residues 408 and 409 (S408/9) subunit, an effect that mimicked their mutation to alanines. Here, we created a mouse which S408/9 have been mutated alanines (S408/9A). S408/9A mice exhibited altered dendritic spine structure,...
The protein p130 was originally isolated from rat brain as an inositol 1,4,5-trisphosphate-binding with a domain organization similar to that of phospholipase C-δ1 but which lacks C activity. Yeast two-hybrid screening human cDNA library for clones encode proteins interact has now led the identification catalytic subunit phosphatase 1α (PP1cα) p130-binding protein. association between and PP1cα also confirmedin vitro by overlay assay, "pull-down" surface plasmon resonance analysis....
The efficacy of synaptic transmission depends on the availability ionotropic and metabotropic neurotransmitter receptors at plasma membrane, but contribution endocytic recycling pathways in regulation gamma-aminobutyric acid type B (GABA(B)) remains controversial. To understand mechanisms that regulate abundance GABA(B) receptors, we have studied their turnover combining surface biotin labeling a microscopic immunoendocytosis assay hippocampal cortical neurons. We report internalization is...
Repeated exposure to psychostimulants induces locomotor sensitization and leads persistent changes in the circuitry of mesocorticolimbic dopamine (DA) system. G-protein-gated inwardly rectifying potassium (GIRK; also known as Kir3) channels mediate a slow IPSC control excitability DA neurons. 5 d decreases size GABA B receptor (GABA R)-activated GIRK currents ( I Baclofen ) ventral tegmental area (VTA) neurons mice, but mechanism underlying this plasticity is poorly understood. Here, we show...
Intravenous anesthetics exert a component of their actions via potentiating inhibitory neurotransmission mediated by γ-aminobutyric type-A receptors (GABA A Rs). Phasic and tonic inhibition is distinct populations GABA Rs, with the majority phasic subtypes composed α1–3βγ2 subunits, whereas dependent on assembled from α4–6βδ subunits. To explore contribution that these forms play in mediating intravenous anesthesia, we have used mice which tyrosine residues 365/7 within γ2 subunit are...
Downregulation of G-protein-coupled receptors (GPCRs) provides an important mechanism for reducing neurotransmitter signaling during sustained stimulation. Chronic stimulation M 2 muscarinic (M Rs) causes internalization R and G-protein-activated inwardly rectifying potassium (GIRK) channels in neuronal PC12 cells, resulting loss function. Here, we show that coexpression GABA B R2 (GBR2s) rescues both surface expression function R, including R-induced activation GIRKs inhibition cAMP...