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Publication : Developmental abnormalities in cortical GABAergic system in mice lacking mGlu3 metabotropic glutamate receptors.

First Author  Imbriglio T Year  2019
Journal  FASEB J Volume  33
Issue  12 Pages  14204-14220
PubMed ID  31665922 Mgi Jnum  J:292850
Mgi Id  MGI:6451219 Doi  10.1096/fj.201901093RRR
Citation  Imbriglio T, et al. (2019) Developmental abnormalities in cortical GABAergic system in mice lacking mGlu3 metabotropic glutamate receptors. FASEB J 33(12):14204-14220
abstractText  Polymorphic variants of the gene encoding for metabotropic glutamate receptor 3 (mGlu3) are linked to schizophrenia. Because abnormalities of cortical GABAergic interneurons lie at the core of the pathophysiology of schizophrenia, we examined whether mGlu3 receptors influence the developmental trajectory of cortical GABAergic transmission in the postnatal life. mGlu3(-/-) mice showed robust changes in the expression of interneuron-related genes in the prefrontal cortex (PFC), including large reductions in the expression of parvalbumin (PV) and the GluN1 subunit of NMDA receptors. The number of cortical cells enwrapped by perineuronal nets was increased in mGlu3(-/-) mice, suggesting that mGlu3 receptors shape the temporal window of plasticity of PV(+) interneurons. Electrophysiological measurements of GABAA receptor-mediated responses revealed a more depolarized reversal potential of GABA currents in the somata of PFC pyramidal neurons in mGlu3(-/-) mice at postnatal d 9 associated with a reduced expression of the K(+)/Cl(-) symporter. Finally, adult mGlu3(-/-) mice showed lower power in electroencephalographic rhythms at 1-45 Hz in quiet wakefulness as compared with their wild-type counterparts. These findings suggest that mGlu3 receptors have a strong impact on the development of cortical GABAergic transmission and cortical neural synchronization mechanisms corroborating the concept that genetic variants of mGlu3 receptors may predispose to psychiatric disorders.-Imbriglio, T., Verhaeghe, R., Martinello, K., Pascarelli, M. T., Chece, G., Bucci, D., Notartomaso, S., Quattromani, M., Mascio, G., Scalabri, F., Simeone, A., Maccari, S., Del Percio, C., Wieloch, T., Fucile, S., Babiloni, C., Battaglia, G., Limatola, C., Nicoletti, F., Cannella, M. Developmental abnormalities in cortical GABAergic system in mice lacking mGlu3 metabotropic glutamate receptors.
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