Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling
- VIB Center for the Biology of Disease, KU Leuven, Belgium
- Centre for Human Genetics, KU Leuven, Belgium
- Leuven Institute for Neuordegenerative Disorders (LIND), KU Leuven, Belgium
- University Hospitals Leuven, Belgium
- KU Leuven, Belgium
- Institute of Neurology, University College London, United Kingdom
Figures
Figure 1 with 1 supplement
Normal cortical layer formation and altered expression of synaptic markers in Aph1bc−/− deficient mice.
(A) Representative pictures of neuronal cortices from Control and Aph1bc−/− null mice at P30 immunostained for the upper layers marker Cux1 and for the pan neuronal marker NeuN. Nuclei were stained …
Figure 1—figure supplement 1
Aph1bc deletion does not affect the expression of inhibitory synaptic markers.
(A) Representative pictures of layer II/III of prefrontal cortices from control and Aph1bc−/− mice at P30 immunolabelled for inhibitory markers VGAT and PV. Scale bar 10 µm. (B and C) Cumulative …
Figure 2
Aph1bc deletion impairs synaptic transmission and plasticity.
(A) Input-Output curves recorded in the Schaffer collaterals of the hippocampus show that basic synaptic transmission is impaired in Aph1bc+/− heterozygous and homozygous Aph1bc−/− mutant mice as …
Figure 3
Spine formation is impaired by single cell Aph1bc-γ-secretase loss of function and is rescued by Nrg1 intracellular signalling.
(A) Representative pictures at DIV15 of cultured hippocampal from Aph1bcfl/fl conditional mutant mice transfected at DIV8 with GFP as control, GFP-ires-Cre to obtain single cell Aph1bc−/− neurons, …
Figure 4
Selective function of different γ-secretase complexes in spine formation.
(A) Cultured hippocampal neurons from Aph1afl/fl conditional mutant mice were transfected at DIV8 with GFP as control or with GFP-ires-Cre to delete Aph1a and fixed at DIV15. (B) Single cell …
Figure 5
Nrg1 intracellular signalling cell-autonomously promotes spine formation in vitro.
(A) Representative pictures of cultured hippocampal neurons transfected at DIV8, at the beginning of synaptogenesis, with either GFP alone as control or GFP and the CRD-Nrg1-Fl, GFP and the Nrg1-ICD …
Figure 6
Aph1bc deletion cell autonomously disrupts spine formation which is rescued by Nrg1-ICD expression in vivo.
(A) Representative drawings of Golgi stained CA1 hippocampal neurons from control and Aph1bc−/− null brains at P30. so, stratum oriens; sp, stratum pyramidale; sr, stratum radiatum; slm, stratum …
