Shank3 absence impairs mGlu5-mediated intracellular calcium release in cortical
neurons. Cortical neuronal cultures were prepared from WT and
Shank3Δ11-/- E17-E18 mouse
embryos. A) Western blot analysis of PSD-enriched fractions of
cortical primary neurons obtained from WT and
Shank3Δ11-/- mice at DIV15. Protein
levels were each normalized against the respective actin control. Data are
expressed as the mean ± SEM of n=3 independent cultures by
genotype. *, p < 0.05. B) At DIV14-15 neurons were loaded
with Fura-2 AM (5 µM, 30 min). After 20 min of de-esterification, the
neurons were challenged with 200 µM DHPG. The results are shown as bar
diagrams. Representative traces of Ca2+ transients are shown at the
left, and the data are expressed as the mean ± SEM of n=127 WT
neurons and n=151 KO neurons that were registered from 18 coverslips (for
each genotype) in three independent cultures. *, p<0.05; **,
p<0.01. C) Representative images of WT and
Shank3Δ11-/- mouse primary cortical
neurons at DIV15. Confocal images were obtained using a Confocal Microscope with
a 63x objective and with sequential-acquisition set at a resolution of 1024 x
1024 pixels. A total of 16 WT and
Shank3Δ11-/- primary cortical neurons at
DIV15 were randomly chosen for quantification from 4 to 10 coverslips from three
independent experiments. Colocalization measurements were performed using
MetaMorph image analysis software. Scale bar 5μm . The histogram shows
the mean ± SEM for the area of Homer clusters over the area of Bassoon
clusters and the area of Homer clusters NOT over Bassoon clusters. *, p <
0.05. D) At DIV12-14 cortical neurons were loaded with Fura-2
and challenged with 200 μM DHPG either in presence (5 min preincubation)
or in absence of of 3 μM CDPPB. Results are shown as bar diagrams.
Representative traces of Ca2+ transients are shown left; data are
expressed as mean ± SEM of n=86 WT neurons and n=77 KO
neurons with vehicle and of n=96 WT neurons and n=95 KO neurons
with CDPPB registered from 18 coverslips (for each conditions) in three
independent cultures for genotype. * p < 0.05; ** p < 0.01.