Browsing by MeSH term "Pyramidal Cells"
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Publication Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling.(Nature Publishing Group, 2010-04-29) Fazzari, Pietro; Paternain, Ana V; Pla, Ramón; Luján, Rafael; Lloyd, Kent; Lerma, Juan; Marín, Oscar; Rico, Beatriz; Valiente, Manuel; Ministerio de Ciencia e Innovación (España); Regional Government of Castile-La Mancha (España); Fundación La Caixa; Unión Europea. Comisión Europea; European Science FoundationSchizophrenia is a complex disorder that interferes with the function of several brain systems required for cognition and normal social behaviour. Although the most notable clinical aspects of the disease only become apparent during late adolescence or early adulthood, many lines of evidence suggest that schizophrenia is a neurodevelopmental disorder with a strong genetic component. Several independent studies have identified neuregulin 1 (NRG1) and its receptor ERBB4 as important risk genes for schizophrenia, although their precise role in the disease process remains unknown. Here we show that Nrg1 and ErbB4 signalling controls the development of inhibitory circuitries in the mammalian cerebral cortex by cell-autonomously regulating the connectivity of specific GABA (gamma-aminobutyric acid)-containing interneurons. In contrast to the prevalent view, which supports a role for these genes in the formation and function of excitatory synapses between pyramidal cells, we found that ErbB4 expression in the mouse neocortex and hippocampus is largely confined to certain classes of interneurons. In particular, ErbB4 is expressed by many parvalbumin-expressing chandelier and basket cells, where it localizes to axon terminals and postsynaptic densities receiving glutamatergic input. Gain- and loss-of-function experiments, both in vitro and in vivo, demonstrate that ErbB4 cell-autonomously promotes the formation of axo-axonic inhibitory synapses over pyramidal cells, and that this function is probably mediated by Nrg1. In addition, ErbB4 expression in GABA-containing interneurons regulates the formation of excitatory synapses onto the dendrites of these cells. By contrast, ErbB4 is dispensable for excitatory transmission between pyramidal neurons. Altogether, our results indicate that Nrg1 and ErbB4 signalling is required for the wiring of GABA-mediated circuits in the postnatal cortex, providing a new perspective to the involvement of these genes in the aetiology of schizophrenia.Publication Localization of the cannabinoid CB1 receptor and the 2-AG synthesizing (DAGLα) and degrading (MAGL, FAAH) enzymes in cells expressing the Ca(2+)-binding proteins calbindin, calretinin, and parvalbumin in the adult rat hippocampus.(Frontiers Media, 2014-06-27) Rivera, Patricia; Arrabal, Sergio; Cifuentes, Manuel; Grondona, Jesús M; Pérez-Martín, Margarita; Rubio, Leticia; Vargas, Antonio; Serrano, Antonia; Pavón, Francisco-Javier; Suárez, Juan; Rodríguez de Fonseca, Fernando; [Rivera,P; Arrabal,S; Vargas,A; Serrano,A; Pavón,FJ; Suárez,J; Rodriguez de Fonseca,F] Laboratorio de Investigación, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Regional Universitario de Málaga (UGC Salud Mental), Málaga, Spain. [Rivera,P; Arrabal,S; Serrano,A; Pavón,FJ; Suárez,J; Rodriguez de Fonseca,F] CIBER OBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain. [Cifuentes,M; Grondona,JM; Pérez-Martín,M] Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga, Málaga, Spain. [Cifuentes,M] CIBER BBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain. [Rubio,L] Departamento de Anatomía y Medicina Legal, Facultad de Medicina, Universidad de Málaga, Málaga, Spain.The retrograde suppression of the synaptic transmission by the endocannabinoid sn-2-arachidonoylglycerol (2-AG) is mediated by the cannabinoid CB1 receptors and requires the elevation of intracellular Ca(2+) and the activation of specific 2-AG synthesizing (i.e., DAGLα) enzymes. However, the anatomical organization of the neuronal substrates that express 2-AG/CB1 signaling system-related molecules associated with selective Ca(2+)-binding proteins (CaBPs) is still unknown. For this purpose, we used double-label immunofluorescence and confocal laser scanning microscopy for the characterization of the expression of the 2-AG/CB1 signaling system (CB1 receptor, DAGLα, MAGL, and FAAH) and the CaBPs calbindin D28k, calretinin, and parvalbumin in the rat hippocampus. CB1, DAGLα, and MAGL labeling was mainly localized in fibers and neuropil, which were differentially organized depending on the hippocampal CaBPs-expressing cells. CB(+) 1 fiber terminals localized in all hippocampal principal cell layers were tightly attached to calbindin(+) cells (granular and pyramidal neurons), and calretinin(+) and parvalbumin(+) interneurons. DAGLα neuropil labeling was selectively found surrounding calbindin(+) principal cells in the dentate gyrus and CA1, and in the calretinin(+) and parvalbumin(+) interneurons in the pyramidal cell layers of the CA1/3 fields. MAGL(+) terminals were only observed around CA1 calbindin(+) pyramidal cells, CA1/3 calretinin(+) interneurons and CA3 parvalbumin(+) interneurons localized in the pyramidal cell layers. Interestingly, calbindin(+) pyramidal cells expressed FAAH specifically in the CA1 field. The identification of anatomically related-neuronal substrates that expressed 2-AG/CB1 signaling system and selective CaBPs should be considered when analyzing the cannabinoid signaling associated with hippocampal functions.