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ISDN2014_0151: Attentional processes, cortisol and emotional states in preadolescent children from different socioeconomic status
Author(s) -
D'Angiulli Amedeo,
Van Roon Patricia,
Schibli Kylie
Publication year - 2015
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2015.04.125
Subject(s) - psychology , citation , socioeconomic status , library science , sociology , computer science , population , demography
The mTOR pathway has been implicated in controlling several aspects of neurodevelopment by regulating the rate of proteinsynthesis. Mutations in the regulatory components Tsc1 and Tsc2 of mTOR-Complex1 (mTORC1) cause Tuberous Sclerosis (TSC) in humans. The majority of TSC patients develop neurological problems including seizures, mental retardation and autism. Recent studies investigated the role of mTOR pathway dys-regulation in excitatory cortical cells, however its role in the development of cortical GABAergic interneurons and the specific contribution of altered GABAergic cells in disease manifestation remain largely unknown. Here, we investigated whether and how Tsc1 knockout perturbs GABAergic circuit development, both in vitro and in vivo. We found that pS6 immunolabeling, a marker of mTORC1 activation, increased specifically in cortical Parvalbumin-positive, basket GABAergic cells (BCs) during the peak of their synaptic maturation phase, between the 2nd and the 4th postnatal week postnatal in vivo. To investigate the role of mTORC1 activation in BC development, we knocked down Tsc1 expression, by transfecting CRE-GFP driven by a promoter specific for BCs in cortical organotypic cultures prepared from Tsc1lox mice. Tsc1 knockdown in vitro caused a precocious increase in bouton density and terminal branching formed by mutant BCs, which was reversed by Rapamycin treatment. These data suggest that mTOR pathway hyperactivation affects the timing of BC synapse maturation. To investigate the role of mTORC1 in GABAergic cells in vivo, we bred Tsc1lox mice with Nkx2.1-CRE mice. Nkx2.1 drives CRE expression in GABAergic neurons derived from the medial ganglionic eminence, which include BCs. At P18, Tsc1fl/fl::Nkx2.1Cre mice showed both mTORC1 hyperactivation in BCs and increased expression of VGAT, a presynaptic GABAergic marker around pyramidal cell somata. These data suggest that BCs may form boutons prematurely in these transgenic mice. Behavioral studies are currently underway to investigate possible deficits in working memory and social behavior.