A5032659348- Neuroscience and Neuropharmacology Research
- Sleep and Wakefulness Research
- Photoreceptor and optogenetics research
- Neural dynamics and brain function
- Memory and Neural Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Circadian rhythm and melatonin
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetics and Neurodevelopmental Disorders
- Sleep and related disorders
- Receptor Mechanisms and Signaling
- Neuroscience of respiration and sleep
- Vestibular and auditory disorders
- EEG and Brain-Computer Interfaces
- Retinal Development and Disorders
- Nicotinic Acetylcholine Receptors Study
- Photochromic and Fluorescence Chemistry
- Anesthesia and Neurotoxicity Research
- Neural Networks and Applications
- Regulation of Appetite and Obesity
- Neuroendocrine regulation and behavior
- Autism Spectrum Disorder Research
- GABA and Rice Research
Tsukuba International University
2014-2025
University of Tsukuba
2014-2025
The University of Texas Southwestern Medical Center
2024
University of Basel
2008-2016
University of Zurich
2002-2008
University of California, San Francisco
1997-2003
Northwestern University
2003
Roche (Switzerland)
2002
Harvard University
2001-2002
Institute of Pharmacology
2002
General anesthetics are widely used in clinical practice. On the molecular level, these compounds have been shown to modulate activity of various neuronal ion channels. However, functional relevance identified sites mediating essential components general anesthetic state, such as immobility and hypnosis, is still unknown. Using gene-targeting technology, we generated mice harboring a subtle point mutation (N265M) second transmembrane region beta3 subunit GABA(A) receptor. In mice,...
The heterogeneity of γ-aminobutyric acid type A (GABA ) receptors contributes to the diversity neuronal inhibition in regulation information processing. Although most GABA are located synaptically, small population α 5 is largely expressed extrasynaptically. To clarify role control behavior, a histidine-to-arginine point mutation was introduced position 105 murine subunit gene, which rendered diazepam-insensitive. Apart from an incomplete muscle relaxing effect, neither sedative,...
Reversing Autism in Mice comprises a heterogeneous group of neurodevelopmental disorders characterized by defects communication and social inter action. A nonsyndromic forms autism is associated with mutations the neuroligin genes, which encode postsynaptic adhesion molecules. Using reversible knockout approach, Baudouin et al. (p. 128 , published online 13 September) investigated vivo functions neuroligin-3 mouse cerebellum. Mutant mice showed major defect metabotropic glutamate...
The functional relevance of brain-derived neurotrophic factor (BDNF) is beginning to be well appreciated not only in mice, but also humans. Because reduced levels typically correlate with impaired neuronal function, increasing BDNF well-tolerated drugs diffusing into the central nervous system may help ameliorating deficits. With this objective mind, we used sphingosine-1 phosphate receptor agonist fingolimod, a drug that crosses blood–brain barrier. In addition, fingolimod has recently been...
The main inhibitory neurotransmitter in the mammalian brain, GABA, mediates multiple forms of signals, such as fast and slow postsynaptic currents tonic inhibition, by activating a diverse family ionotropic GABA A receptors (GABA Rs). Here, we studied whether distinct R subtypes mediate these various inhibition using approach mice carrying point mutation α-subunit rendering individual insensitive to diazepam without altering their sensitivity expression receptors. Whole cell patch-clamp...
Significance Narcolepsy-cataplexy is a debilitating disorder characterized by excessive daytime sleepiness (sleep attacks) and cataplexy, sudden bilateral loss of muscle tone often triggered emotion. The disease caused selective hypothalamic neurons producing the neuropeptide orexin. Currently, only symptomatic therapies are available for narcolepsy. Here, we examine pharmacological effect YNT-185, nonpeptide, agonist orexin type-2 receptor in mouse models narcolepsy-cataplexy. We show that...
GABAergic transmission regulates adult neurogenesis by exerting negative feedback on cell proliferation and enabling dendrite formation outgrowth. Further, synapses target differentiating dentate gyrus granule cells prior to of glutamatergic connections. GABAA receptors (GABAARs) mediating tonic (extrasynaptic) phasic (synaptic) are molecularly functionally distinct, but their specific role in regulating is unknown. Using global single-cell targeted gene deletion subunits contributing the...
Abstract Exercise can improve sleep by reducing latency and increasing slow-wave (SWS). Some studies, however, report adverse effects of exercise on architecture, possibly due to a wide variety experimental conditions used. We examined the effect quality using standardized parameters novel analytical methods. In cross-over intervention study we 60 min vigorous at 60% $$\dot{V}{\text{O}}_{2}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mover> <mml:mi>V</mml:mi>...
Mossy fiber synapses form the major excitatory input into autoassociative network of pyramidal cells in CA3 area hippocampus. Here we demonstrate that at mossy synapses, glutamate and γ-aminobutyric acid (GABA) act as autaptic heterosynaptic presynaptic inhibitory transmitters through metabotropic receptors (mGluRs) GABA B receptors, respectively. Both mGluRs are activated spillover from adjacent synapses. We caused by brief tetanic activation terminals remains intact physiological...
Recent evidence suggests that internal calcium stores and calcium-induced release (CICR) provide an important source of drives short-term presynaptic plasticity at central synapses. Here we tested for the involvement CICR in six excitatory synapses acute rat hippocampal cerebellar brain slices. Depletion with thapsigargin prevention ryanodine have no effect on paired-pulse facilitation, delayed neurotransmitter, or calcium-dependent recovery from depression. Fluorometric measurements also...
Cholinergic innervation of the hippocampus has been implicated in memory formation and retrieval. Here we study cholinergic modulation excitatory transmission CA3 area rat hippocampus. We used a combination optical measurements presynaptic calcium electrophysiological synaptic currents to associational-commissural (A/C) mossy fiber (MF) synapses brain slices. Direct mediated by ACh receptors is only evident at A/C synapse, where inhibition primarily reflects channel muscarinic receptors. MF...
Hippocampal long-term potentiation (LTP) represents the cellular response of excitatory synapses to specific patterns high neuronal activity and is required for learning memory. Here we identify a mechanism that requires calcium-binding protein Copine-6 translate initial calcium signals into changes in spine structure. We show recruited from cytosol dendrites postsynaptic membranes by transients precede LTP. Cpne6 knockout mice are deficient hippocampal LTP, neurons knockouts lack structural...
Optochemistry, an emerging pharmacologic approach in which light is used to selectively activate or deactivate molecules, has the potential alleviate symptoms, cure diseases, and improve quality of life while preventing uncontrolled drug effects. The development in-vivo applications for optochemistry render brain cells photoresponsive without relying on genetic engineering been progressing slowly. nucleus accumbens (NAc) a region regulation slow-wave sleep (SWS) through integration...
Long-term potentiation (LTP) is the most prominent model for molecular and cellular mechanisms of learning memory. Two main forms LTP have been distinguished. The N -methyl- d -aspartate-receptor-dependent studied extensively, whereas much less known about -aspartate-receptor-independent LTP. This latter type was first described at mossy fiber synapses in hippocampus subsequently parallel cerebellum as well corticothalamic synapses. These presynaptic require a rise intraterminal calcium...
Abstract The physiological significance of the large diversity GABA A receptors is poorly understood. Using mice, which carry a point mutation that renders specific subtypes diazepam insensitive, it was recently discovered particular types are involved in specific, behaviorally relevant signaling pathways. We have used these mice to study inhibitory synaptic transmission amygdala. receptor‐mediated postsynaptic currents (IPSCs) per se were not affected by mutations. Their modulation...
Synapse formation and maintenance require extensive transsynaptic interactions involving multiple signal transduction pathways. In the cerebellum, Purkinje cells (PCs) receive GABAergic, axo-dendritic synapses from stellate axo-somatic basket cells, both with GABA A receptors containing α1 subunit. Here, we investigated effects of a targeted deletion subunit gene on GABAergic synaptogenesis in PCs, using electrophysiology immunoelectron microscopy. Whole-cell patch-clamp recordings acute...
Neuronal signal integration as well synaptic transmission and plasticity highly depend on the morphology of dendrites their spines. Nogo-A is a membrane protein enriched in adult central nervous system (CNS) myelin, where it restricts capacity axons to grow regenerate after injury. also expressed by certain neurons, particular during development, but its physiological function this cell type less understood. We addressed question cerebellum, transitorily Purkinje cells (PCs) early postnatal...
Sleep loss increases AMPA-synaptic strength and number in the neocortex. However, this is only part of synaptic sleep response. We report increased AMPA/NMDA EPSC ratio frontal-cortical pyramidal neurons layers 2-3. Silent synapses are absent, decreasing plastic potential to convert silent NMDA active AMPA synapses. These changes recovered by sleep. genes enriched for shaping cellular components controlling glutamate synapse phenotype, overlap with autism risk primarily observed excitatory...