Figure 7.

Postsynaptic Loss of CYFIP1 In Vivo Increases Inhibitory Synaptic Function

(A) Representative recordings of miniature inhibitory postsynaptic currents (mIPSCs) (–70 mV) in CA1 pyramidal cells from P28–P34 control floxed (left) and CYFIP1^NEX cKO mice (right). Lower panels are representative sections of recordings (contiguous 0.3-s segments).

(B) Pooled data showing increase mIPSC mean amplitude in CYFIP1^NEX cKO mice (cKO) (from 23.8 ± 1.8 to 30.3 ± 2.2 -pA; n = 13–14 cells; p = 0.0288) but no change in frequency (from 3.3 ± 0.3 to 3.7 ± 0.3 Hz; n = 13–15 cells; p = 0.324, n.s.) All Student’s t test. Box-and-whisker plots indicate median (line), 25th to 75th percentiles (box), and range of data within 1.5× interquartile range (IQR) of box (whiskers) and mean (open circles).

(C) Cumulative frequency graphs of mIPSC amplitude (left) and frequency (right).

(D) Graphs of mIPSC kinetics showing no change in rise and decay time (rise time: from 5.2 ± 0.3 to 5.3 ± 0.4 ms; n = 13–14 cells; p = 0.935, n.s.; decay time: 9.2 ± 0.6 to 10.1 ± 0.4 ms; n = 13–15 cells; p = 0.247, n.s.; both Student’s t test).

(E) Representative recordings of miniature excitatory postsynaptic currents (mEPSCs) (–70 mV) in CA1 pyramidal cells from P28–P34 control floxed (left) and CYFIP1^NEX cKO mice (right). Lower panels are representative sections of recordings (contiguous 0.3-s segments).

(F) Pooled data showing no change in mEPSC mean amplitude (from 19.2 ± 1.4 to 18 ± 1.4 -pA; n = 21–22 cells; p = 0.549, n.s.) and frequency between control (Ctrl) and CYFIP1 cKO mice (cKO) (from 1.5 ± 0.2 to 1.3 ± 0.2 Hz; n = 18–20 cells; p = 0.565, n.s.). All Student’s t test. Box-and-whisker plots indicate median (line), 25th to 75th percentiles (box), and range of data within 1.5× IQR of box (whiskers) and mean (open circles).

(G) Cumulative frequency graphs of mEPSC amplitude (left) and frequency (right).

(H) Graphs of mEPSC kinetics showing no change in rise and decay time (rise time: from 4.7 ± 0.2 to 5 ± 0.3 ms; n = 22 cells; p = 0.527, n.s.; decay time: from 6.7 ± 0.2 to 6.7 ± 0.2 ms; n = 22 cells; p = 0.8415, n.s.; both Student’s t test).

(I) Pooled data showing an increase in mIPSC mean charge transfer in CYFIP1^NEX cKO (cKO) mice compared to floxed control (Ctrl) (from 1 ± 0.2 to 1.7 ± 0.2 pC; n = 13–14 cells; p = 0.0067) but no change in mEPSC mean charge transfer (from 0.3 ± 0.1 to 0.3 ± 0.03 pC; n = 18–20 cells; p = 0.753, n.s.) All Student’s t test. Box-and-whisker plots indicate median (line), 25th to 75th percentiles (box), and range of data within 1.5× IQR of box (whiskers) and mean (open circles).

(J) The probability curve of mean mEPSC and mIPSC charge transfer in CYFIP1^NEX cKO mice as a percentage of control mice highlighting the imbalance between excitation and inhibition in CYFIP1^NEX cKO animals.

^∗p < 0.05; ^∗∗p < 0.01. Bar graph bars indicate mean, and error bars indicate SEM. See also Figure S4.