Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
Alpha7 nicotinic acetylcholine receptors (nAChRs) are promising novel targets for the treatment of neurocognitive disorders. Although the cognitive enhancer potential of alpha7 nAChR agonists and positive allosteric modulators (PAMs) has been confirmed in several preclinical animal models, there are only sparse in vivo electrophysiological data on their effects on the firing activity and excitability of neurons. The present study investigated and compared local effects of alpha7 nAChR agonist PHA-543613 and PAMs PNU-120596 and NS-1738 on the spontaneous and N-methyl-D-aspartate-evoked (NMDA-evoked) firing rate of rat CA1 hippocampal pyramidal cells, in vivo. Furthermore, effects of alpha7 nAChR antagonist methyllycaconitine (MLA) and GABA were also tested. Results showed substantially different effects of the alpha7 nAChR agonist and PAMs. While PNU-120596 and NS-1738 predominantly and significantly increased both spontaneous and NMDA-evoked firing rate of the neurons, application of PHA-543613 resulted in almost equal distribution of facilitatory and inhibitory effects. The increase of the NMDA-evoked firing rate exerted by NS-1738 was superadditive over the sum of the single effects of NMDA and NS-1738. The simultaneous application of alpha7 nAChR agonist PHA-543613 and PAM NS-1738 resulted in additive increase of both spontaneous and NMDA-evoked firing rate. However, NS-1738 counteracted inhibitory effects of PHA-543613 in 5 out of 6 neurons, resulting in a synergistic potentiation of their firing responses to NMDA. Our results suggest that alpha7 nAChR PAMs increase neuronal excitability more potently than agonists, while the remarkable occurrence of inhibitory effects of PHA-543613 (possibly originating from receptor desensitization) implies that agonists may exert neuroprotective effects.
Pubmed ID: 31249369
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
American chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented on July 16, 2013. The NeuroLOG consortium is addressing: *Management and access of partly structured data, heterogeneous and distributed in an open environment. *Access control and protection of private medical data. *Control of workflows implied in complex computing process on grid infrastructures. *Extraction and quantification of relevant parameters for different pathologies: Multiple sclerosis, Brain Vascular Stroke, Brain tumors Four application pipelines have been proposed in the context of the project. The pipelines are formalized using the Scufl data flow language. *Multiple Sclerosis image analysis pipelines *Brain Stroke application pipeline (from GIN) *Stroke / tumours Anacom application pipeline (from IFR49) Different softwares developed and/or used in this project are presented.
View all literature mentionsLab interested in understanding how neuronal circuitries of the brain support its cognitive capacities. Its goal is to provide rational, mechanistic explanations of cognitive functions at a descriptive level. In the lab''s view, the most promising area of cognitive faculties for scientific inquiry is memory, since it is a well-circumscribed term, can be studied in animals and substantial knowledge has accumulated on the molecular mechanisms of synaptic plasticity. Available software: * NeuroScope: NeuroScope can display local field potentials (EEG), neuronal spikes, behavioral events, as well as the position of the animal in the environment. It also features limited editing capabilities. * Klusters: Klusters is a powerful and easy-to-use cluster cutting application designed to help neurophysiologists sort action potentials from multiple neurons on groups of electrodes (e.g., tetrodes or multisite silicon probes). * KlustaKwik: KlustaKwik is a program for automatic cluster analysis, specifically designed to run fast on large data sets. * MATLAB m-files: A selection of MATLAB files developed in the lab.
View all literature mentions