Article Figures & Data
Figures
- Figure 1.
Loss of Fmr1 disrupts the normal development of cell-to-cell connectivity mediated by AMPA:KA-Rs in L5a. A, Example traces from pre- (A1) and postsynaptic neurons (A2, A3, A4) demonstrating two connections of a possible three as observed by average uEPSCs. B–D, Connectivity frequency (B1, B2), frequency of connections being part of a “one-way” or “two-way” connection (C1, C2), and uEPSC amplitude (D1, D2) are plotted for WT (1) and Fmr1 KO (2) slices. Numbers in plots are total number of possible connections (B) and sample number (D). In C, #'s and *'s apply to one- vs two-way and P15 vs P30 comparisons, respectively. In D, medians are indicated. E, Percent change in connectivity (Conn) and median amplitude (Amp) in the P15→P30 interval. F, Replot of B for comparison between genotypes. *p < 0.05; **p < 0.01; ***p < 0.001 for all figures. Error bars in B, C, and F indicate 95% confidence interval.
- Figure 2.
Postsynaptic Fmr1 regulates the development of cell-to-cell connectivity mediated by AMPA:KA-Rs. A, B, Connectivity frequency (A1, A2), and uEPSC amplitude (B1, B2) are plotted for postsynaptic WT (1) and Fmr1 KO (2) cells in mosaic slices. C, Percent change in connectivity (Conn) and median amplitude (Amp) in the P15→P30 interval. D, Connectivity frequency based on postsynaptic (replot of A) and presynaptic FMRP expression. E–G, Short-term plasticity, CV, 20/80 rise-time, and decay time constant of uEPSCs are all unchanged in Fmr1 KO neurons (see Materials and Methods). In E–G, numbers in parentheses indicate n (P15, P30).
- Figure 3.
Connectivity frequency is unchanged with postsynaptic Fmr1 deletion at P15 when incorporating an increase in “silent,” NMDAR-mediated connections. A, Example average uEPSCs that are AMPA:KA-R mediated (top) and silent (bottom). B, C, Connectivity frequency based on AMPA:KA-R-mediated currents (B) and on silent, NMDAR only, connections (C). D, Total connectivity based on adding B and C. E, uEPSC amplitude of silent connections. F, AMPA:KA-R/NMDAR ratio of uEPSCs that were not silent (one WT and two KO uEPSCs had no detectable NMDAR-mediated response and are not included). G, Idealized schematic of our data showing the connectivity of L5A pyramidal neurons through development, which depends on postsynaptic expression of FMRP. This schematic incorporates both silent and AMPA:KA-R-mediated connections and the gray box indicates the estimated time window of exuberant silent connections with Fmr1 deletion. Error bars in B–D indicate 95% confidence interval; in E and F, error bars indicate SEM.
- Figure 4.
Postsynaptic FMRP's role in connectivity pruning is not observed in mEPSCs. A, Example traces of mEPSCs obtained from the mosaic mouse. B, C, mEPSC data from mosaic mice did not show either the WT pruning or the pruning deficit with postsynaptic Fmr1 deletion in the P15→P30 window. mEPSC frequency (B) and amplitude (C) are shown. Although differences are shown for 1 week epochs, none are observed in the context of the P15→P30 interval. Error bars indicate SEM.
