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Fig. 5 | Molecular Autism

Fig. 5

From: Tsc1 haploinsufficiency in Nkx2.1 cells upregulates hippocampal interneuron mTORC1 activity, impairs pyramidal cell synaptic inhibition, and alters contextual fear discrimination and spatial working memory in mice

Fig. 5

Impairment of synaptic inhibition of pyramidal cells by Nkx2.1 interneurons. a Diagram of experimental paradigm with AAV2/9-DIO-ChR2-EYFP injection and pyramidal cell recording in slices from Nkx2.1Cre/wt;Tsc1f/wt mutant and Nkx2.1Cre/wt control mice. b Representative fluorescence images of EYFP-positive Nkx2.1 cells in CA1 hippocampus showing similar ChR2-EYFP expression in mutant and control mice. Scale bars in top images also applies to bottom images. c, d Representative traces (c) and summary graph (d) of input-output function of IPSCs evoked in CA1 pyramidal cells by optogenetic stimulation of Nkx2.1 interneurons in slices from Nkx2.1Cre/wt;Tsc1f/wt mutant (red) and Nkx2.1Cre/wt control (black) mice. IPSC amplitude is reduced in mutant compared to control mice (n = 12 cells in 6 Wt mice (Nkx2.1Cre/wt;Tsc1wt/wt) and 10 cells in 6 Tg mice (Nkx2.1Cre/wt;Tsc1f/wt); 2-way ANOVA, *p < 0.05). e Diagram of experimental paradigm with AAV2/9-DIO-ChR2-EYFP injection and recordings from EYFP-expressing Nkx2.1 interneurons in CA1 hippocampus. f, g Representative traces (f) and summary graph (g) of input-output function of Nkx2.1 interneuron action potential firing evoked by optogenetic stimulation in slices from Nkx2.1Cre/wt;Tsc1f/wt mutant (red) and control (black) mice. Activation of Nkx2.1 interneurons is similar in mutant and control mice (n = 9 cells in Wt and 6 cells in Tg mice; 2-way ANOVA, p > 0.05)

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