In several neuronal types of the CNS, glutamate and GABA receptors mediate a persistent current which reflects the presence of a low concentration of transmitters in the extracellular space. Here, we further characterize the tonic current mediated by ambient glutamate in rat hippocampal slices. A tonic current of small amplitude (53.99 +/- 6.48 pA at +40 mV) with the voltage dependency and the pharmacology of NMDA receptors (NMDARs) was detected in virtually all pyramidal cells of the CA1 and subiculum areas. Manipulations aiming at increasing D-serine or glycine extracellular concentrations failed to modify this current indicating that the glycine binding sites of the NMDARs mediating the tonic current were saturated. In contrast, non-transportable inhibitors of glutamate transporters increased the amplitude of this tonic current, indicating that the extracellular concentration of glutamate primarily regulates its magnitude. Neither AMPA/kainate receptors nor metabotropic glutamate receptors contributed significantly to this tonic excitation of pyramidal neurons. In the presence of glutamate transporter inhibitors, however, a significant proportion of the tonic conductance was mediated by AMPA receptors. The tonic current was unaffected when inhibiting vesicular release of transmitters from neurons but was increased upon inhibition of the enzyme converting glutamate in glutamine in glial cells. These observations indicate that ambient glutamate is mainly of glial origin. Finally, experiments with the use-dependent antagonist MK801 indicated that NMDARs mediating the tonic conductance are probably extra-synaptic NMDARs.
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http://dx.doi.org/10.1113/jphysiol.2006.123570 | DOI Listing |
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Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy.
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Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00185 Rome, Italy.
Refractory angina pectoris (RAP) is a clinical syndrome characterized by persistent chest pain caused by myocardial ischemia that is unresponsive to optimal pharmacological therapy and revascularization procedures. Spinal cord stimulation (SCS) has emerged as a promising therapeutic option for managing RAP, offering significant symptom relief and improved quality of life. A systematic literature review was conducted to evaluate the clinical effectiveness, mechanisms of action, and safety profile of SCS in treating RAP.
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Global Health Research Group in Acquired Brain and Spine Injuries, Cambridge, UK.
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Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston MA 02115.
The concentrations of extracellular and intracellular signaling molecules, such as dopamine and cAMP, change over both fast and slow timescales and impact downstream pathways in a cell-type specific manner. Fluorescence sensors currently used to monitor such signals are typically optimized to detect fast, relative changes in concentration of the target molecule. They are less well suited to detect slowly-changing signals and rarely provide absolute measurements of either fast and slow signaling components.
View Article and Find Full Text PDFEpilepsy Behav
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Physiology Department, Ribeirão Preto, School of Medicine, University of São Paulo, (USP), Ribeirão Preto, Brazil; Neuroscience and Behavioral Sciences Department, Ribeirão Preto, School of Medicine, University of São Paulo, (USP), Ribeirão Preto, Brazil. Electronic address:
Epilepsies are complex neurological entities usually co-existing with neuropsychiatric comorbidities. We already demonstrated that microinjection of oxytocin (OT) into the central nucleus of amygdala (CeA) induces hypergrooming in Wistar rats, a model of compulsion. Furthermore, the Wistar Audiogenic Rat (WAR) strain is a genetic model of generalized tonic-clonic seizures.
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