Gamma-aminobutyric acid A receptor (GABA(A)R)-mediated postsynaptic currents (IPSCs) were recorded from dopaminergic neurons of the ventral tegmental area of young rats in acute brain slices and from mechanically dissociated neurons. Low... more
Gamma-aminobutyric acid A receptor (GABA(A)R)-mediated postsynaptic currents (IPSCs) were recorded from dopaminergic neurons of the ventral tegmental area of young rats in acute brain slices and from mechanically dissociated neurons. Low concentrations (0.1-0.3 microm) of muscimol, a selective GABA(A)R agonist, increased the amplitude, and reduced the paired pulse ratio of evoked IPSCs. Moreover, muscimol increased the frequency but not the amplitude of spontaneous IPSCs (sIPSCs). These data point to a presynaptic locus of muscimol action. It is interesting that 1 microm muscimol caused an inhibition of sIPSCs, which was reversed to potentiation by the GABA(B) receptor antagonist CGP52432. Isoguvacine, a selective GABA(A)R agonist that belongs to a different class, mimicked the effects of muscimol on sIPSCs: it increased them at low (<or= 0.5 microm), and decreased them at a higher concentration (1 microm). Hence, the activation of presynaptic GABA(A)Rs facilitates GABA release, ...
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To explore the potential biochemical mechanisms of neuromuscular junction transmission (NMJT) dysfunction induced by organophosphorus insecticides. Ten rats were dosed with phoxim (1,144 mg/kg) and 5 of them developed myasthenia. The NMJT... more
To explore the potential biochemical mechanisms of neuromuscular junction transmission (NMJT) dysfunction induced by organophosphorus insecticides. Ten rats were dosed with phoxim (1,144 mg/kg) and 5 of them developed myasthenia. The NMJT function was evaluated by the mean consecutive differences (MCD) measured by stimulation single fiber electromyography (SSFEMG) with the frequency of stimuli at 20 Hz. The activity of Ca(2+)-ATPase, Na(+), K(+)-ATPase, cAMP dependent protein kinase (PKA), Ca(2+)/phospholipid dependent protein kinase (PKC), and tyrosine protein kinase (TPK) were determined. In comparison with the control and non-myasthenic rats, the results in myasthenic rats showed that: (1) the MCDs increased; (2) the activities of Ca(2+)-ATPase, Na(+), K(+)-ATPase and PKA decreased and were negatively correlated with MCD; (3) the activities of PKC and TPK increased, and were positively correlated with MCD; (4) the phosphorylation of serine residuals in sarcolemma was weaker and t...
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Research Interests: Cognitive Science, Calcium, Patch-clamp and imaging techniques, Hippocampus, Learning and Memory, and 18 moreBrain, Animals, Calcium channels, Male, Lead, Calcium Channel, Central Nervous System, Synaptic Transmission, Neurons, Cadmium, Rats, Wistar Rats, Tetrodotoxin, Action potential, Neurosciences, Bicuculline, Gamma-Aminobutyric Acid, and Whole cell Patch-Clamp
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Research Interests: Fluorescence Microscopy, Motor Control, Drug Discovery, Confocal Microscopy, Patch-clamp and imaging techniques, and 15 moreCell line, Learning and Memory, Mutation, Mice, Animals, Endoplasmic Reticulum, Drug Screening, Nicotinic Acetylcholine Receptors, Acetylcholine, Molecular cloning, Fluorescent Protein, Transfection, BIOCHEMICAL PHARMACOLOGY, Ligands, and Cell Membrane
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Mesencephalic astrocyte-derived neurotrophic factor (MANF) - one of a new class of astrocyte-derived human proteins - selectively promotes the survival of dopamine neurons of the ventral midbrain. Using the whole-cell clamp technique, we... more
Mesencephalic astrocyte-derived neurotrophic factor (MANF) - one of a new class of astrocyte-derived human proteins - selectively promotes the survival of dopamine neurons of the ventral midbrain. Using the whole-cell clamp technique, we looked for acute effects of ...
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Research Interests: Cognitive Science, Electrophysiology, Membrane Proteins, Hippocampus, Brain, and 17 moreAnimals, Calcium channels, Synaptic Transmission, Acidification, Neurons, Rats, Sodium channel, Rat, Voltage-Gated Sodium Channels, Hydrogen-Ion Concentration, Protons, Neurosciences, Extracellular, Extracellular Space, Patch Clamp, Gamma-Aminobutyric Acid, and Calcium Channel Blockers
The physiological and pharmacological properties of taurine-induced responses were investigated in dopaminergic (DA) neurones from the ventral tegmental area (VTA) of young rats aged 1-13 postnatal days, either in acute brain slices or... more
The physiological and pharmacological properties of taurine-induced responses were investigated in dopaminergic (DA) neurones from the ventral tegmental area (VTA) of young rats aged 1-13 postnatal days, either in acute brain slices or acutely dissociated neurones. When whole-cell responses were recorded from current-clamped neurones using the gramicidin-perforated technique, the application of taurine (0.01-30 mm) accelerated firings and induced membrane depolarization. In voltage-clamped neurones, taurine induced a current which was antagonized by strychnine and by picrotoxin, but not by bicuculline. In addition, taurine-induced current showed complete cross-desensitization with glycine-activated currents but not with gamma-aminobutyric acid (GABA)-activated currents. Thus, taurine is a full agonist of the glycine receptors (GlyRs) in the VTA. Further studies found that taurine acted mainly on non-synaptic GlyRs. The application of 20 microm bicuculline abolished the spontaneous i...
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The glutamatergic subthalamic nucleus (STN) exerts control over motor output through nuclei of the basal ganglia. High-frequency electrical stimuli in the STN effectively alleviate motor symptoms in movement disorders, and cholinergic... more
The glutamatergic subthalamic nucleus (STN) exerts control over motor output through nuclei of the basal ganglia. High-frequency electrical stimuli in the STN effectively alleviate motor symptoms in movement disorders, and cholinergic stimulation boosts this effect. To gain knowledge about the mechanisms of cholinergic modulation in the STN, we studied cellular and circuit aspects of nicotinic acetylcholine receptors (nAChRs) in mouse STN. We discovered two largely divergent microcircuits in the STN; these are regulated in part by either α4β2 or α7 nAChRs. STN neurons containing α4β2 nAChRs (α4β2 neurons) received more glutamatergic inputs, and preferentially innervated GABAergic neurons in the substantia nigra pars reticulata. In contrast, STN neurons containing α7 nAChRs (α7 neurons) received more GABAergic inputs, and preferentially innervated dopaminergic neurons in the substantia nigra pars compacta. Interestingly, local electrical stimuli excited a majority (79%) of α4β2 neuro...
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Research Interests: Neuropsychopharmacology, Dopamine, Glutamate, Vitamin D receptor, Animals, and 13 morePropionic Acid, Ethanol, Drug Addiction, Synaptic Transmission, Neurons, Positive Feedback, Rats, Ventral Tegmental Area, Reserpine, Glutamic Acid, Raclopride, Excitatory Postsynaptic Potentials, and Glutamate release
Research Interests: Genetics, Cognitive Science, Animal Behavior, Caenorhabditis elegans, Drug interactions, and 16 moreGene expression, Mice, Animals, Male, Amphetamine, Transgenic Animals, Neurons, Time Factors, Neuron, Chloride Channel, Action Potentials, Neurosciences, Ivermectin, Motor activity, Molecular Sequence Data, and Corpus striatum
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Research Interests: Cognitive Science, Electrophysiology, Spinal Cord Injury, Cell separation, Patch-clamp and imaging techniques, and 22 moreCerebrospinal Fluid, Brain, Animals, Spinal Cord, Cell Death, Ethanol, Central Nervous System, Rat Brain, Neurons, Brain injury, Glycerol, Rats, Ventral Tegmental Area, Electrodes, Voltage Clamp, Statistical Methods for Neuroscience, Cell Survival, Sodium Chloride, Neurosciences, Patch Clamp, Gramicidin, and Excitatory Postsynaptic Potentials
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Research Interests: Fluorescence Microscopy, Motor Control, Drug Discovery, Confocal Microscopy, Patch-clamp and imaging techniques, and 15 moreCell line, Learning and Memory, Mutation, Mice, Animals, Endoplasmic Reticulum, Drug Screening, Nicotinic Acetylcholine Receptors, Acetylcholine, Molecular cloning, Fluorescent Protein, Transfection, BIOCHEMICAL PHARMACOLOGY, Ligands, and Cell Membrane
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Probing the neural circuit dynamics underlying behaviour would benefit greatly from improved genetically encoded voltage indicators. The proton pump Archaerhodopsin-3 (Arch), an optogenetic tool commonly used for neuronal inhibition, has... more
Probing the neural circuit dynamics underlying behaviour would benefit greatly from improved genetically encoded voltage indicators. The proton pump Archaerhodopsin-3 (Arch), an optogenetic tool commonly used for neuronal inhibition, has been shown to emit voltage-sensitive fluorescence. Here we report two Arch variants with enhanced radiance (Archers) that in response to 655 nm light have 3-5 times increased fluorescence and 55-99 times reduced photocurrents compared with Arch WT. The most fluorescent variant, Archer1, has 25-40% fluorescence change in response to action potentials while using 9 times lower light intensity compared with other Arch-based voltage sensors. Archer1 is capable of wavelength-specific functionality as a voltage sensor under red light and as an inhibitory actuator under green light. As a proof-of-concept for the application of Arch-based sensors in vivo, we show fluorescence voltage sensing in behaving Caenorhabditis elegans. Archer1's characteristics ...