0005, one-way ANOVA compared to the −20 ms data set, n = 5–8 per pairing interval), similar to the ∼2-fold increase in PSP size when GABAR antagonists were applied under baseline conditions. This indicates that the timing dependence for the suppression of inhibition is closely tuned to the optimal −20 ms pairing interval that elicits ITDP. The specificity with which ITDP reduces the SC-evoked IPSP versus the PP-evoked IPSP suggests that ITDP does not depress inhibition globally. Given that inhibition is highly compartmentalized with nonoverlapping

Trametinib price populations of INs targeting the CA1 PN soma and dendrites (Klausberger and Somogyi, 2008), we next asked whether soma- or dendrite-targeting INs were regulated learn more by ITDP. Whole-cell current-clamp recordings obtained separately from CA1 PN soma and apical dendrites (∼250 μm from the soma in SR) showed that induction of ITDP caused a much smaller increase in the SC-evoked dendritic

SC PSP (1.44-fold ± 0.04-fold change; p < 0.001, n = 5) than in the somatic SC PSP (2.61-fold ± 0.22-fold change; p < 0.001, n = 7; p < 0.005, dendrite versus soma, t test; Figures 3B and 3C). The PP-evoked dendritic PSP was unaltered during ITDP (p = 0.5083), similar to the somatic PP PSP. The small size of dendritic ITDP is surprising, as the induction of ITDP requires summation of PP and SC PSPs, which should be greatest in the PN dendrite. Might the difference between somatic and dendritic ITDP

arise from a differential suppression of inhibition at the two compartments? In support of this idea, we found that dendritic ITDP was not altered when GABARs were blocked continuously throughout the experiment (p = 0.812, dendritic SC ITDP, control versus +SR, CGP; Figures 3B2 and 3B3). This contrasts with the large decrease in somatic ITDP during GABAR blockade (Figures 3C2 and 3C3). These results suggest that dendritic ITDP results almost exclusively from SC eLTP, which is similar in size to the SC eLTP at the soma. Although it may seem surprising that the increased somatic SC PSP during ITDP does not passively propagate to cause TCL a larger increase in the dendritic SC PSP (Figures 3B3–3C3), our computational model confirms that a selective loss of somatic inhibition does not significantly boost the local dendritic PSP evoked by SC inputs (Figure S2). Next, we used optogenetics to identify the specific class of perisomatic-targeting interneurons involved in ITDP. We focused on the two major IN classes known to target the CA1 PN soma and perisomatic dendrites: the PV and CCK basket cells (Freund and Katona, 2007). We used a recombinant adeno-associated virus (rAAV) to express channelrhodopsin-2 fused to EYFP (ChR2-EYFP) (Boyden et al., 2005) selectively in cells that expressed Cre recombinase. Injection of this virus (rAAV-DIO-EF1α-ChR2-EYFP; Zhang et al.