In many neuronal types, backpropagating action potentials (APs) are critically involved in the induction of synaptic plasticity. We manipulated AP backpropagation and investigated its role in synaptic plasticity in L5 pyramidal neurons in acute neocortical brain slices taken from P14-21 Sprague-Dawley rats. Paired recordings were made at 34°C with presynaptic pyramidal neurons in L2/3 or in L5. The location of putative synaptic contacts, confirmed anatomically in some cases using 2-photon laser scanning microscopy of dye-filled cells and/or bright-field microscopy of fixed and histologically processed neurons, indicated that 20-80% EPSP rise time (RT) predicts input location accurately (r=0.89). L2/3-to-L5 synapses tended to be more distal than their L5-to-L5 counterparts, as indicated by RT: 3.0±0.4 versus 2.0±0.2 ms (mean±SEM, p<0.05; Student's t test). Pairing APs and EPSPs (5 at 50 Hz, +10 ms post-pre relative timing difference) reliably evoked typical Hebbian LTP at proximal inputs (RT3 ms; 80±5%, n=26; p1.0 mV; 140±6%, n=14; p<0.001). Similarly, dendritic depolarizing current injection rescued LTP of weak distal EPSPs (<1.0 mV; 163±6.7%, n=5; p<0.001). Both conditions may evoke LTP because backpropagating APs are boosted by depolarization (Stuart & Häusser, 2001). In agreement, supralinear Ca²⁺ signals — measured with 2-photon laser scanning microscopy as the change in Fluo-5F signal normalized to Alexa 594 fluorescence — were generated throughout the distal dendritic tree by pairing APs with large EPSPs (percent of linear sum=200±30%, n=37, p<0.001), or with dendritic depolarizing current injection (368±68%, n=19, p<0.001), but not with small EPSPs (98±8%, n=9; 0.37±0.2mV). Ca²⁺ signal supralinearity increased with distance from the soma, ranging from 20% proximally to 500% at 900 µm from the soma, and the distance-dependence was described by a power law. Interestingly, for distal inputs synaptic stimulation alone, but not APs alone, resulted in LTD (70±6%, n=10 vs 102±6%, n=10; p<0.01). This type of LTD was abolished by the cannabinoid receptor CB1 blocker AM251 (0.9 µM; 99±3%, n=6; p<0.01). Our results indicate that long-term plasticity rules in L5 pyramidal neurons depend on dendritic location of the synapses, and that cooperative synaptic input or dendritic depolarization can switch plasticity between LTD and LTP by boosting backpropagation of action potentials. This activity-dependent switch provides a mechanism for associative learning across different neocortical layers that process distinct types of information.