Figure 3.

Homer1 KO synaptic plasticity deficits can be rescued by rAAV-Homer1c. (A and C) A low dose of rAAV-Homer1c (A; n = 6(4)), but not a high dose (C; n = 11(3)) was able to recover the late phase LTP deficit exhibited by H1-KO mice (n = 6(3)) after HFS. (B and D) LTP elicited by TBS was also rescued in H1-KO (n = 7(3)) with the low dose vector (B; n = 5(3)) but not by the high dose vector rAAV-H1c (D; n = 12(4)). Low dose rAAV-H1c was not only able to recover both early and late phase TBS LTP, but also shows a trend for enhanced induction and LTP over that displayed by LM-WT. (E) Illustrates the significant difference in synaptic transmission of the high dose H1c slices when compared to the other experimental groups as determined by the I/O relationship. One arrow points to 33% of stimulus intensity, where similar responses for all experimental groups are observed. The 50% arrow indicates the stimulus intensity at which most of the experiments were carried out. KO+H1c 1.2×10¹¹(n = 44(9)), KO+H1c 2.4×10¹⁰ (n = 28(7)), LM-WT (n = 51(14)), H1-KO (n = 48(12)) (F) KO animals display normal PPF when compared to LM-WT (same n values as for I/O curve). At brief interstimulus inter-trials, high dose KO+H1 animals display depression relative to the other experimental groups, while low dose KO+H1 mice show an enhancement in PPF compared to the other groups. (G and H) Using 33% stimulation intensity, the LTP deficits of H1-KO slices injected with high dose H1c showed recovery of LTP function. (G) HFS-LTP: KO+H1c 1.2×10¹¹ at 33% max (n = 6(3)). (H) TBS-LTP KO+H1c 1.2×10¹¹ at 33% max (n = 11(5)). (A, B, C, D, G, H - Top): Representative EPSPs for each experimental group are shown (left: 4mins prior to stimulation, right: 180 min after stimulation). Calibration 1 mV, 1 ms.