Neuronal excitotoxicity during stroke is caused by activation of unidentified large-conductance channels, leading to swelling and calcium dysregulation. We show that ischemic-like conditions [O 2 /glucose deprivation (OGD)] open hemichannels, or half gap junctions, in neurons. Hemichannel opening was indicated a large linear current flux across the membrane small fluorescent molecules. Single-channel openings hemichannels (530 picosiemens) were observed OGD. Both dye blocked inhibitors...

Cortical spreading depression (SD) is a propagating wave of neuronal and glial depolarization that manifests in several brain disorders. However, the relative contribution neurons astrocytes to SD genesis has remained controversial. This part due lack utilizing sophisticated experimental methodologies simultaneously quantify multiple cellular parameters. To address this, we used simultaneous two-photon imaging, intrinsic optical electrophysiological recordings ascertain changes processes are...

Spreading depression (SD) is a slowly propagating neuronal depolarization that underlies certain neurologic conditions. The wave-like pattern of its propagation suggests SD arises from an unusual form communication. We used enzyme-based glutamate electrodes to show during induced by transiently raising extracellular K(+) concentrations ([K(+)]o) in rat brain slices, there was rapid increase the concentration required vesicular exocytosis but unlike fast synaptic transmission, still occurred...

Two-photon laser scanning microscopy has revolutionized the ability to delineate cellular and physiological function in acutely isolated tissue vivo. However, there exist barriers for many laboratories acquire two-photon microscopes. Additionally, if owned, typical systems are difficult modify rapidly evolving methodologies. A potential solution these problems is enable scientists build their own high-performance adaptable system by overcoming a resource insufficiency. Here we present...

Abstract Maintaining a proper balance between the glutamate receptor-mediated neuronal excitation and A type of GABA receptor (GABA R) mediated inhibition is essential for brain functioning; its imbalance contributes to pathogenesis many disorders including neurodegenerative diseases mental illnesses. Here we identify novel glutamate-GABA R interaction by direct binding R. In HEK293 cells overexpressing recombinant Rs, analog ligands, while producing no current on their own, potentiate...

Airway mucus overproduction is one of the most common symptoms asthma that causes severe clinical outcomes in patients. Despite effectiveness general therapies, specific treatments prevent patients remain lacking. Recent studies have found activation GABAA receptors (GABAAR) important for promoting oversecretion lung airway epithelia. Here, we report luteolin, a natural flavonoid compound, suppresses by functionally inhibiting GABAergic system. This hypothesis was investigated testing...

Allergic asthma is a lifelong airway condition that affects people of all ages. In recent decades, prevalence continues to increase globally, with an estimated number 250,000 annual deaths attributed the disease. Although inhaled corticosteroids and β-adrenergic receptor agonists are primary therapeutic avenues effectively reduce symptoms, profound side effects may occur in patients long-term treatments. Therefore, development new strategies needed as alternative or supplement current...

Adenosine is arguably the most potent and widespread presynaptic modulator in CNS, yet adenosine receptor signal transduction pathways remain unresolved. Here, we demonstrate a novel mechanism which A 1 stimulation leads to p38 mitogen-activated protein kinase (MAPK) activation contributes inhibition of synaptic transmission. Western blot analysis indicated that selective [with N 6 -cyclopentyladenosine (CPA)] resulted rapid increases phosphorylated (phospho-p38) MAPK immunoreactivity...

The hippocampus creates a cognitive map of the external environment by encoding spatial and self-motion-related information. However, it is unclear whether hippocampal neurons could also incorporate internal states reflecting an animal's exploratory intention, which not driven rewards or unexpected sensory stimuli. In this study, subgroup CA1 was found to encode both information animals' investigatory intentions in male mice. These became active before initiation exploration behaviors at...

Spreading depression (SD) is a pathophysiological phenomenon characterized by propagating waves of profound neuronal and glial depolarization in central nervous system gray matter. Although SD primarily mediated neurons with subsequent astrocytic response, it remains unclear how activity modulated after altered astrocyte signaling contribute to excitability. Here, we report that the concurrent Ca2+ wave, enhanced promoting secondary period oscillations. SD-induced oscillations did not...

Spreading depolarization (SD) represents a neurological process characterized by massive, self-sustaining wave of brain cell depolarization. Understanding its mechanism is important for treating ischemic or hemorrhagic stroke and migraine with aura. Many believed that ion fluxes through NMDA receptors (NMDARs) are responsible neuronal transmembrane currents SD. However, the explicit role NMDARs remains ambiguous. This in part due to limitation traditional pharmacological approaches resolving...

Hyperekplexia is a neurological disorder associated primarily with mutations in the α1 subunit of glycine receptors (GlyRs) that lead to dysfunction glycinergic inhibitory transmission. To date, most identified result disruption surface expression or altered channel properties α1-containing GlyRs. Little evidence has emerged support an involvement allosteric GlyR modulation human hyperekplexia. Here, we report recombinant GlyRs containing α1β subunits missense mutation (W170S), previously...

Abstract Epilepsy and spreading depolarization (SD) are both episodic brain disorders often exist together in the same individual. In CA1 pyramidal neurons of mouse hippocampal slices, induction SD evoked epileptiform activities, including ictal-like bursts, which occurred during repolarizing phase SD, subsequent generation paroxysmal shifts (PDSs), characterized by mild plateau with overriding spikes. The duration activity was correlated recovery time potential whereas parameters PDSs were...

Abstract Modulation of the A type γ-aminobutyric acid receptors (GABA R) is one major drug targets for neurological and psychological diseases. The natural flavonoid compound luteolin (2-(3,4-Dihydroxyphenyl)- 5,7-dihydroxy-4-chromenone) has been reported to have antidepressant, antinociceptive anxiolytic-like effects, which possibly involve mechanisms modulating GABA signaling. However, as yet detailed studies pharmacological effects are still lacking, we investigated on recombinant...

Hyperekplexia, an inherited neuronal disorder characterized by exaggerated startle responses with unexpected sensory stimuli, is caused dysfunction of glycinergic inhibitory transmission. From analysis newly identified human hyperekplexia mutations in the glycine receptor (GlyR) α1 subunit, we found that alanine-to-proline missense mutation (A384P) resulted substantially higher desensitization level and lower agonist sensitivity homomeric GlyRs when expressed HEK cells. The incorporation β...

NMDA receptors (NMDAR) are voltage- and glutamate-gated heteromeric ion channels found at excitatory neuronal synapses, the functions of which to mediate mechanisms brain plasticity and, thereby, its higher order functions. In addition Glu, activation these requires Gly or d-Ser as a coagonist. However, it is not fully known why coagonism required for opening NMDAR channels. We show herein that ligand binding domains (LBD) GluN1 GluN2A subunits heterodimerize only when both coagonists, Glu...

The dynamic vascular responses during cortical spreading depolarization (CSD) are causally related to pathophysiological consequences in numerous neurovascular conditions, including ischemia, traumatic brain injury, cerebral hemorrhage, and migraine. Monitoring of the hemodynamic penetrating vessels CSD is motivated understand mechanism neurological disorders. Six SD rats were used, craniotomy surgery was performed before imaging. CSDs induced by topical KCl application. Ultrasound ultrafast...

Abstract Tactile sensors with capability of multiaxial force perception play a vital role in robotics and human–machine interfaces. Flexible optical waveguide have been an emerging paradigm tactile sensing due to their high sensitivity, fast response, antielectromagnetic interference. Herein, flexible sensor enabled by U‐shaped micro/nanofibers (MNFs) is reported. The MNF embedded within elastomer film topped dome‐shaped protrusion. When the protrusion subjected vector forces, undergoes...

ii TABLE OF CONTENTS iv LIST TABLES vii FIGURES viii ABBREVIATIONS x ACKNOWLEDGEMENTS xi DEDICATION xii CO-AUTHORSHIP STATEMENT xiii