(A, B): A strong form of LTD that expressed the protein synthesis dependent late phase of LTD (L-LTD) was induced by paired pulses of low frequency stimulation (PP-1Hz: 50 msec interpulse interval at 1 Hz for 15 min) in the basal (A, dark gray circles, n = 6) and apical (B, dark gray circles, n = 6) dendritic compartments. Conversely, a weak form of LTD that expressed the protein synthesis independent early phase of LTD (E-LTD) was induced after a single train of low frequency stimulation (1 Hz: 1 train of 15 min at 1 Hz) in the basal (A, light gray circles, n = 5) and apical (A, light gray circles, n = 5) dendritic compartments. Blockage of new protein synthesis transformed strong LTD into weak LTD in the basal (A, open circles, n = 6) and apical (B, open circles, n = 6) dendritic compartments (anisomycin, an inhibitor of translation, was added between −20 min and +20 min of recording). (C, D): A strong form of LTP that expressed the late phase of LTP (L-LTP) was induced by 4 trains of high frequency stimulation (HFS, 4 trains of 1-sec at 100 Hz stimulation, 5 min inter-train interval) in the basal (C, dark gray circles, n = 6) and apical (D, dark gray circles, n = 6) dendritic compartments. Like with strong LTD, blockage of new protein synthesis transformed strong LTP into weak LTP that expressed the early phase of LTP in the basal (C, open circles, n = 6) and apical (D, open circles, n = 6) dendritic compartments (anisomycin was added between −20 min and +20 min of recording). S1 and S2 represent independent afferents synapsing on basal or apical dendrites, respectively.

(A): Strong LTD induced in the apical pathway S1 remains unaltered (top blue trace), while the subsequent expression of strong LTP induced in the apical pathway S2 is reduced (bottom blue trace). Time interval between inductions is 45 min. To facilitate visualization of the interference, the expression of control (unpaired) strong LTD (top) and strong LTP (bottom) is shown in all panels (grey traces). (B): Reversing the roles produces an even stronger interference. Strong LTP induced in the apical pathway S2 (bottom blue trace) blocks the subsequent expression of strong LTD induced in the apical pathway S1 (top blue trace). Time interval between inductions is 45 min. (C): The interference of strong LTD (apical pathway S1, top blue trace) over the expression of strong LTP (apical pathway S2, bottom blue trace) is much more substantial with a shorter time interval between inductions (15 min). (D): With the same time interval (15 min), strong LTP (apical pathway S2, bottom blue trace) blocks the subsequent expression of strong LTD (apical pathway S1, top blue trace). (E): Despite the apparent dominance of the interference of LTP over LTD, simultaneous induction of strong LTD (apical pathway S1, top blue trace) and strong LTP (apical pathway S2, bottom blue trace) results in reduced expression of LTP. (F): Graphs representing LTP change (top) and LTD change (bottom) indexes (see text for details). Negative time intervals correspond to the change in the first induced form of synaptic plasticity, positive time intervals correspond to the change in the second (subsequent) form of synaptic plasticity. Note that either LTP or LTD when first induced shows an index change around 1 (no interference). In contrast, LTP and LTD change indexes are smaller than 1 (interference) for the second induced form of plasticity. Also note that as the time interval between inductions increases the magnitude of interference (measured as the LTP or LTD change) decreases for the second induced form of plasticity. At time interval 0 min, LTP change is smaller than 1, while LTD change is about 1. Each independent data set was obtained from 6 mice. S1 and S2 represent independent afferents synapsing on the apical dendritic compartment. Representative traces are shown (gray: control; dark gray: interaction; 1: baseline, 2 after synaptic plasticity induction). Scale bar is 2 mV and 5 msec. Enlarged traces are shown in Fig. S1.

(A): Absence of interference between strong LTD induced in the basal dendritic compartment (pathway S1, top blue trace) and strong LTP induced in the apical dendritic compartment (pathway S2, bottom blue trace). Time interval between inductions is 45 min. To facilitate visualization of interference, the expression of control (unpaired) strong LTD (top) and strong LTP (bottom) is shown in all panels (grey traces). (B): Similarly, strong LTP induced in the apical pathway S2 (bottom blue trace) does not interfere with the subsequent expression of strong LTD induced in the basal pathway S1 (top blue trace). Time interval between inductions is 45 min. (C): A mild interference of strong LTD (basal pathway S1, top blue trace) over the expression of strong LTP (apical pathway S2, bottom blue trace) is observed with a 15 min time interval between inductions. (D): A modest interference is also observed for strong LTP (apical pathway S2, bottom blue trace) over the expression of strong LTD (basal pathway S1, top blue trace) with a 15 min time interval. (E): In spite of the observed mild transcompartmental interference, simultaneous induction of strong LTD (basal pathway S1, top blue trace) and strong LTP (apical pathway S1, bottom blue trace) results in blockage of the expression of strong LTD. (F): Graphs representing LTP change (top) and LTD change (bottom) indexes (see text for details). Negative time intervals correspond to the change in the first induced form of synaptic plasticity, positive time intervals correspond to the change in the second (subsequent) form of synaptic plasticity. Similar to the intracompartmental studies, when first induced, LTP and LTD change indexes show values close to 1 (no interference). LTP and LTD change indexes are smaller than 1 (interference) for the second induced form of plasticity only at 15 min. time interval, as no interaction was observed at 45 min. time interval (LTP and LTD change index∼1). At time interval 0 min, LTD change is smaller than 1, while LTP change is about 1. Each independent data set was obtained from 6 mice. S1 and S2 represent independent afferents synapsing on the basal and the apical dendritic compartments. Representative traces are shown (gray: control; dark gray: interaction; 1: baseline and 2: after synaptic plasticity induction). Scale bar is 2 mV and 5 msec. Enlarged traces are shown in Fig. S2.

(A): Failure to induce a cooperative interaction (the conversion of weak LTD into strong LTD) between strong LTP induced in apical pathway S2 (bottom blue trace) and weak LTD induced in apical pathway S1 (top blue trace) with a 45 min time interval between inductions. However with a 90 min time interval between inductions (red traces), cooperative interaction is observed. (B): Absence of cooperative interaction between strong LTP and weak LTD across dendritic compartments. Weak LTD induced in the S1 basal pathway (top panel) is not transformed into strong LTD after induction of strong LTP in the apical pathway S1 (bottom panel) with either, a 45 min (blue traces) or a 90 min (red traces) time interval between inductions. (C): Graphs representing the LTP change (top) and LTD change (bottom) indexes for the intracompartmental interaction between a strong form of LTP and a weak form of LTD. An absence of a cooperative effect is evidenced by LTP and LTD change indexes close to 1. In contrast, an LTD change index higher than 1 demonstrated a cooperative effect between LTP and LTD with a time interval of 90 min. The LTP change index remained close to 1. (D): Graphs representing the LTP change (top) and LTD change (bottom) indexes for the transcompartmental interaction between a strong form of LTP and a weak form of LTD. No deviation from 1 is observed for the LTP or LTD change index at 45 or 90 min time interval; demonstrating the absence of cooperative interaction between LTP and LTD across dendritic compartments. In all the figures each independent data set was obtained from 6 mice. S1 and S2 represent two independent afferents synapsing on the apical (A) or on the basal and the apical dendritic compartment, respectively (B).

Absence of intracompartmental interference between strong LTP (apical pathway S2, bottom red trace) and strong LTD (apical pathway S1; top red trace) with a 90 min time interval between inductions. The expression of control (unpaired) strong LTD (top) and strong LTP (bottom) is shown in the gray traces. Compare with the intracompartmental interference observed with a 45 min time interval between inductions (Fig. 2B). Also compare the interference observed with a 15 min time interval and with a 45 min time interval between inductions across dendritic compartments (e.g. Fig. 3D vs. Fig. 3A). Each independent data set was obtained from 6 mice. S1 and S2 represent independent afferents synapsing on the apical dendritic compartment.

Within the same dendritic compartment: (A): Disruption of the expression of strong LTP (apical pathway S2, bottom gray trace) by the protein synthesis blocker anisomycin (20 µM, horizontal bar) prevents the interference over the subsequent expression of strong LTD (apical pathway S1, top gray trace). Time interval between inductions is 45 min. To facilitate visualization of the rescue of the interference, the expression of the interaction between strong LTP and strong LTD in normal rACSF (without blockers) is shown in light blue traces in all panels. (B): Disruption of the expression of strong LTP (apical pathway S2, bottom hollow trace) by the transcription blocker actinomycin (40 µM, horizontal bar) did not prevent the interference over the subsequent expression of strong LTD (apical pathway S1, top hollow trace). Time interval between inductions is 45 min. Across dendritic compartments. (C): Disruption of the expression of strong LTP (apical pathway S2, bottom gray trace) by anisomycin (horizontal bar) did not significantly prevent the interference over the subsequent expression of strong LTD (basal pathway S1, top gray trace). Time interval between inductions is 15 min. (D): Disruption of the expression of strong LTP (apical pathway S2, bottom hollow trace) by actinomycin (horizontal bar) did not significantly prevent the interference over the subsequent expression of strong LTD (basal pathway S1, top hollow trace). Time interval between inductions is 15 min. In all the figures each independent data set was obtained from 6 mice. S1 and S2 represent two independent afferents synapsing on the apical (A, C) or on the basal and the apical dendritic compartment, respectively (B, D).

(A): Graph representing the Plasticity Index (LTP change × LTD change for any given interaction) from all intracompartmental experiments carried out in this study. Despite the nature of the plasticity, the first form of plasticity remains largely unaffected (negative time intervals) compared to the second form of plasticity (positive time intervals). Remarkably, as interference between LTP and LTD wanes off (15, 45 and 90 min. time intervals, blue lines), cooperative interactions could be seen (45, 90 min time interval, red line). (B) Graph representing the Plasticity Index (LTP change × LTD change for any given interaction) from all transcompartmental experiments carried out in this study. Similar to intracompartmental interactions, irrespective of the nature of the plasticity, the first form of plasticity remains largely unaffected (negative time intervals) compared to the second form of plasticity (positive time intervals). Also similar to intracompartmental interactions, interference between LTP and LTD wanes off with the lengthening of the time interval between inductions (15 and 45 min. time intervals, blue lines), but no cooperative interactions were seen (45, 90 min time interval, red line) once interference subsided. Graphs in A and B highlight four main findings of our study: 1) that only the subsequent form of synaptic plasticity is affected, 2) that the strength of the interaction depends on the time separation between inductions, 3) that cooperation and interference can not occur at the same time intervals, and 4) that intracompartmental interactions are stronger in magnitude than transcompartmental ones. A fifth finding of our study is the dependency on new protein synthesis for the intracompartmental interference between LTP and LTD. (C): Proposed model for the mechanistic switch from interfering to cooperative interactions between LTP and LTD within the same dendritic compartment. We suggest that newly synthesized protein modulate the interaction between LTP and LTD in a temporally and spatially restricted fashion. The figure exemplifies the interaction between a strong form of LTP (L-LTP) and a strong form of LTD (L-LTD). We hypothesized that a limited amount of protein factors induced by either of these two types of synaptic plasticity would constrain other synapses localized within the same dendrites from consolidating an opposite form of synaptic plasticity. Once the activity of these protein factors has weakened, cooperative interactions (i.e. in this example capture of LTD) are allowed by the productively use of common plasticity proteins.