A5058016799- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Ion channel regulation and function
- Cannabis and Cannabinoid Research
- Sleep and Wakefulness Research
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neural Engineering
- Photoreceptor and optogenetics research
- Memory and Neural Mechanisms
- Adenosine and Purinergic Signaling
- Molecular Sensors and Ion Detection
- Neurological Complications and Syndromes
- Neuroscience of respiration and sleep
- Receptor Mechanisms and Signaling
- Synthesis and Properties of Aromatic Compounds
- Neuroinflammation and Neurodegeneration Mechanisms
- Tuberous Sclerosis Complex Research
- Natural Compound Pharmacology Studies
- Nicotinic Acetylcholine Receptors Study
- Advanced Memory and Neural Computing
- Photochromic and Fluorescence Chemistry
- Biomedical Research and Pathophysiology
- Plant Molecular Biology Research
- Biological and pharmacological studies of plants
- Genetic Neurodegenerative Diseases
Oregon Health & Science University
2018-2023
VA Portland Health Care System
2017-2023
Inserm
2011-2018
Institut de Neurobiologie de la Méditerranée
2011-2018
Aix-Marseille Université
2011-2018
Pulmonary and Critical Care Associates
2017
Neurochlore (France)
2014
OZ Biosciences (France)
2014
Bogomoletz Institute of Physiology
1995-2009
National Academy of Sciences of Ukraine
2000-2006
We report that the oxytocin-mediated neuroprotective γ-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in valproate and fragile X rodent models of autism. During subsequently, hippocampal neurons these have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, gamma oscillations. Maternal pretreatment with bumetanide restored offspring control electrophysiological behavioral phenotypes. Conversely, blocking...
During development, formation of topographic maps in sensory cortex requires precise temporal binding thalamocortical networks. However, the physiological substrate for such synchronization is unknown. We report that early gamma oscillations (EGOs) enable spatiotemporal neonatal rat whisker system. Driven by a thalamic oscillator and initially independent cortical inhibition, EGOs synchronize neurons single barreloid corresponding barrel support plasticity at developing synapses. propose...
Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized the presence of brain malformations, cortical tubers that are thought to contribute generation pharmacoresistant epilepsy. Here we report tuberless heterozygote Tsc1+/− mice show functional upregulation GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (<P19)....
In conditions of facilitated synaptic release, CA3/CA1 synapses generate anomalously slow NMDA receptor-mediated EPSCs (EPSC(NMDA)). Such a time course has been attributed to the cooperation through glutamate spillover. Imitating natural pattern activity, we have applied short bursts (2-7 stimuli) high-frequency stimulation and observed spike-to-spike slow-down EPSC(NMDA) kinetics, which accompanied facilitation. It was found that early component burst-induced late distinct pharmacological...
Presynaptic action potential spikes control neurotransmitter release and thus interneuronal communication. However, the properties dynamics of presynaptic in neocortex remain enigmatic because boutons are small direct patch-clamp recordings have not been performed. Here, we report from neocortical pyramidal neurons interneurons. Our data reveal rapid large potentials layer 5 fast-spiking interneurons reliably propagating into axon collaterals. For in-depth analyses, establish mature cultured...
At many central synapses, endocannabinoids released by postsynaptic cells act retrogradely on presynaptic G-protein-coupled cannabinoid receptors to inhibit neurotransmitter release. Here, we demonstrate that cannabinoids may directly affect the functioning of inhibitory glycine receptor (GlyR) channels. In isolated hippocampal pyramidal and Purkinje cerebellar neurons, endogenous anandamide 2-arachidonylglycerol, applied at physiological concentrations, inhibited amplitude altered kinetics...
Altered development of the human cerebral cortex can cause severe malformations with often intractable focal epileptic seizures and may participate in common pathologies, notably epilepsy. This raises important conceptual therapeutic issues. Two missense mutations sushi repeat-containing protein SRPX2 had been previously identified disorders or without structural developmental alteration speech cortex. In present study, we aimed to decipher precise role SRPX2, have a better knowledge on...
<i>N</i>-Methyl-d-aspartate (NMDA) receptor antagonists that are highly selective for specific NMDA 2 (NR2) subunits have several potential therapeutic applications; however, to date, only NR2B-selective been described. Whereas most glutamate binding site display a common pattern of NR2 selectivity, NR2A > NR2B NR2C NR2D (high low affinity), (2<i>S</i>*,3<i>R</i>*)-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid (PPDA) has selectivity NR2C- and NR2D-containing receptors. A...
Cannabinoids are known to regulate inhibitory synaptic transmission via activation of presynaptic G protein-coupled cannabinoid CB1 receptors (CB1Rs). Additionally, recent studies suggest that cannabinoids can also directly interact with recombinant GABAA (GABAARs), potentiating currents activated by micromolar concentrations γ-aminobutyric acid (GABA). However, the impact this direct interaction on GABAergic inhibition in central nervous system is unknown. Here we report mediated GABAARs...
Increasing extracellular [Ca2+] ([Ca2+]o) strongly decreases intrinsic excitability in neurons but the mechanism is unclear. By one hypothesis, [Ca2+]o screens surface charge, reducing voltage-gated sodium channel (VGSC) activation and by another activates Calcium-sensing receptor (CaSR) closing sodium-leak (NALCN). Here we report that neocortical from CaSR-deficient (Casr-/-) mice had more negative resting potentials did not fire spontaneously reduced divalent-containing solution (T0.2)...
At chemical synapses, voltage-activated calcium channels (VACCs) mediate Ca 2+ influx to trigger action potential-evoked neurotransmitter release. However, the mechanisms by which regulates spontaneous transmission have not been fully determined. We shown that VACCs are a major of release at neocortical inhibitory synapses but excitatory suggesting fundamental differences in neurotransmission GABAergic and glutamatergic synapses. Recently, VACC blockers were reported reduce glutamate it was...
When performed at increased external [Ca2+]/[Mg2+] ratio (2.5 mM/0.5 mM), temporary block of A1 adenosine receptors in hippocampus [by 8-cyclopentyltheophylline (CPT)] leads to a dramatic and irreversible change the excitatory postsynaptic current (EPSC) evoked by Schaffer collateral/commissural (SCC) stimulation recorded situ patch clamp CA1 pyramidal neurons. The duration EPSC becomes stimulus dependent, increasing with increase strength. later occurring component is carried through...
Endogenous cannabinoid signaling is vital for important brain functions, and the same pathways can be modified pharmacologically to treat pain, epilepsy, posttraumatic stress disorder. Endocannabinoid-mediated changes excitability are predominantly attributed 2-arachidonoylglycerol (2-AG) acting presynaptically via canonical receptor, CB1. Here, we identify a mechanism in neocortex by which anandamide (AEA), another major endocannabinoid, but not 2-AG, powerfully inhibits somatically...
Despite almost forty years of widespread use antidepressant drugs, their mode action is still unknown. Hyperforin, a phloroglucinol derivative, major pharmacologically and therapeutically active constituent Hypericum perforatum extract that widely used as an herbal drug. However, the mechanism or mechanisms these naturally abundant, non-toxic extracts remain unclear. Enzymatically isolated patch-clamped rat central peripheral neurons exposed to rapid changes in composition external medium...
Cellular electrophysiological signatures of Parkinson's disease described in the pharmacological 6-hydroxydopamine (6-OHDA) animal models include spontaneous repetitive giant GABAergic currents a subpopulation striatal medium spiny neurons (MSNs), and rhythmic bursts spikes generated by subthalamic nucleus (STN) neurons. We investigated whether similar are present Pink1 −/− mice, genetic rodent model PARK6 variant disease. Although 9- to 24-month-old mice show reduced dopamine content...
Endocannabinoids are known as retrograde messengers, being released from the postsynaptic neuron and acting on specific presynaptic G-protein-coupled cannabinoid (CB) receptors to decrease neurotransmitter release. Also, at physiologically relevant concentrations cannabinoids can directly modulate function of voltage-gated receptor-operated ion channels. Using patch-clamp recording we analyzed consequences direct action an endocannabinoid, 2-arachidonoylglycerol (2-AG), functional properties...
Direct electrical recordings from conventional boutons in the mammalian central nervous system have proven challenging due to their small size. Here, we provide a protocol for direct whole-cell patch-clamp presynaptic of primary dissociated cultured neurons rodent neocortex. We describe steps prepare neocortical cultures and recording pipettes, followed by identifying establishing bouton recording. then details on precise pipette capacitance compensation required high-resolution...
Voltage-gated sodium channels (VGSCs) are strategically positioned to mediate neuronal plasticity because of their influence on action potential waveform. VGSC function may be strongly inhibited by local anesthetic and antiepileptic drugs modestly modulated via second messenger pathways. Here, we report that the allosteric modulators calcium-sensing receptor (CaSR) cinacalcet, calindol, calhex, NPS 2143 completely inhibit current in vast majority cultured mouse neocortical neurons. This form...
Previously, we have described the modulatory effect of diadenosine polyphosphates Ap4A and Ap5A on synaptic transmission in rat hippocampal slices mediated by presynaptic receptors (Klishin et al., 1994). In contrast, now describe how nonhydrolyzable analog diadenosine-5',5'''-P1,P4-[beta,beta'-methylene]tetraphosphate (AppCH2ppA) at low micromolar concentrations exerts strong nondesensitizing inhibition orthodromically evoked field potentials (OFPs) without affecting amplitude excitatory...
USING an in situ patch clamp hippocampal CA1 minislices, we measured excitatory postsynaptic currents (EPSC) by varying the strength of stimulus applied to axons CA3 neurones. The kinetics EPSC was initially independent strength. Postischaemic potentiation observed 60–80 min after brief periods (10 min) anoxia/aglycaemia. decay slowed significantly most examined In 11 17 cells became dependent on strength: a slower corresponded stronger stimulus. This effect not abolished...