A5040199904- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Receptor Mechanisms and Signaling
- Lipid Membrane Structure and Behavior
- Stress Responses and Cortisol
- Epilepsy research and treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Photoreceptor and optogenetics research
- Neuropeptides and Animal Physiology
- Neurology and Historical Studies
- Nerve injury and regeneration
- Pharmacological Receptor Mechanisms and Effects
- Anesthesia and Neurotoxicity Research
- Neural dynamics and brain function
- Cellular transport and secretion
- Neurotransmitter Receptor Influence on Behavior
- Genetic Neurodegenerative Diseases
- Cannabis and Cannabinoid Research
- Signaling Pathways in Disease
- Hereditary Neurological Disorders
- Pharmacological Effects and Toxicity Studies
- Neurobiology and Insect Physiology Research
- Neurogenetic and Muscular Disorders Research
- Muscle Physiology and Disorders
- ATP Synthase and ATPases Research
Janssen (Belgium)
2016-2020
Janssen (United States)
2016-2019
University of California, Los Angeles
2012
University of Pennsylvania
2003-2011
Howard Hughes Medical Institute
2006
Members of the <i>α</i>-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA) subtype ionotropic glutamate receptors mediate majority fast synaptic transmission within mammalian brain and spinal cord, representing attractive targets for therapeutic intervention. Here, we describe novel AMPA receptor modulators that require presence accessory protein CACNG8, also known as transmembrane regulatory <i>γ</i>8 (TARP-<i>γ</i>8). Using calcium flux, radioligand binding, electrophysiological...
Mammalian neuromuscular junctions are useful model synapses to study the relationship between synaptic structure and function, although these have rarely been studied together at same synapses. To do this, we generated transgenic lines of mice in which thy1.2 promoter drives expression synaptopHluorin (spH) as a means optically measuring vesicle distribution release. SpH is colocalized with other proteins presynaptic terminals does not alter normal function. Nerve stimulation leads readily...
Neurotrophin-dependent activation of the tyrosine kinase receptor trkB.FL modulates neuromuscular synapse maintenance and function; however, it is unclear what role alternative splice variant, truncated trkB (trkB.T1), may have in peripheral axis. We examined this question trkB.T1 null mice demonstrate that vivo performance nerve-evoked muscle tension are significantly increased. In vitro assays indicated gain-in-function trkB.T1(-/-) animals resulted specifically from an increased...
Prolonged exposure to abnormally high calcium concentrations is thought be a core mechanism underlying hippocampal damage in epileptic patients; however, no prior study has characterized activity during seizures the live, intact hippocampus. We have directly investigated this possibility by combining whole-brain electroencephalographic (EEG) measurements with microendoscopic imaging of pyramidal cells CA1 region freely behaving mice treated pro-convulsant kainic acid (KA). observed that KA...
The serine hydrolase monoacylglycerol lipase (MAGL) is the rate-limiting enzyme responsible for degradation of endocannabinoid 2-arachidonoylglycerol (2-AG) into arachidonic acid and glycerol. Inhibition 2-AG leads to elevation 2-AG, most abundant endogenous agonist cannabinoid receptors (CBs) CB1 CB2. Activation these has demonstrated beneficial effects on mood, appetite, pain, inflammation. Therefore, MAGL inhibitors have potential produce therapeutic in a vast array complex human...
Axonal degeneration is the major cause of permanent neurological disability in individuals with inherited diseases myelin. and neuronal changes that precede axonal degeneration, however, are not well characterized. We show here dysmyelinated lower motor neurons retract regenerate dysfunctional presynaptic terminals, leading to severe before degeneration. In addition, dysmyelination led a decreased synaptic quantal content, an indicator dysfunction. The amplitude rise time miniature endplate...
The hippocampus, a structure essential for spatial navigation and memory undergoes anatomical functional changes during chronic stress. Here, we investigate the effects of stress on ability place cells to encode neural representation linear track. To model physiological conditions hippocampal function, transgenic mice expressing genetically encoded calcium indicator GCaMP6f in CA1 pyramidal neurons were chronically administered with 40 µg/ml cortisol 8 weeks. Cortisol-treated exhibited...
Recently, our group along with another demonstrated that GPR139 can be activated by L-phenylalanine (L-Phe) and L-tryptophan (L-Trp) at physiologically relevant concentrations. is discretely expressed in brain, highest expression medial habenula. Not only are the endogenous ligands catecholamine/serotonin precursors, but expressing areas directly/indirectly regulate activity of neurons. Thus, appears an interconnected circuit involved mood, motivation, anxiety. The aim this study was to...
Imaging neuronal activity in awake behaving mice with miniature fluorescence microscopes requires the implementation of a variety procedures. Surgeries are performed to gain access cell population interest and implant microscope components. After recovery period, trained exhibit desired behavior. Finally, is imaged synchronized that To take full advantage technology, selection calcium indicator experimental design must be carefully considered. In this article, we explain procedures...
Introduction Blockade of GluN2B (NR2B)‐containing NMDA receptors has been proposed as a therapy for number neurological and psychiatric diseases including mood disorders. A antagonists have identified developed over the last three decades. These compounds, however, significant limitations in regard to their selectivity or drug‐like properties (e.g. oral bioavailability). Methods The pharmacology JNJ‐63612445 was explored using in‐vitro assays (calcium mobilization, competitive radioligand...