A co-operative switch determines the sign of synaptic plasticity in distal dendrites of neocortical pyramidal neurons


Per Jesper Sjöström & Michael Häusser

Wolfson Institute for Biomedical Research and Department of Physiology, University College London, London WC1E 6BT, UK


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 34C with presynaptic pyramidal neurons in L2/3 or in L5. The location of putative synaptic contacts, confirmed anatomically in some cases, 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: 3.00.4 versus 2.00.2 ms (p<0.05). Pairing APs and EPSPs (5 at 50 Hz, +10 ms pre-post relative timing difference) reliably evoked typical Hebbian LTP at proximal inputs (RT<3ms; after/before=1365%, n= 43), but surprisingly produced LTD at distal synapses (RT>3ms; 805%, n=26; p<0.001). However, distal LTP was rescued by EPSPs larger than those produced by typical unitary inputs (>1.0 mV; 1406%, n=14; p<0.001). Similarly, dendritic depolarizing current injection rescued LTP of weak distal EPSPs (<1.0 mV; 1636.7%, n=5; p<0.001). Both conditions may evoke LTP because backpropagating APs are boosted by depolarization (1). In agreement, supralinear Ca2+ signals were generated throughout the distal dendritic tree by pairing APs with large EPSPs (percent of linear sum=20030%, n=37, p<0.001), or with dendritic depolarizing current injection (368 68%, n = 19, p < 0.001), but not with small EPSPs (988%, n=9; 0.370.2mV). Ca2+ signal supralinearity increased with distance from the soma, ranging from 20% proximally to 500% at 900 m 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 (706%, n=10 vs 1026%, n=10; p<0.01). This type of LTD was abolished by the cannabinoid receptor CB1 blocker AM251 (0.9 M; 993%, 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.


Supported by the Wellcome Trust, EU, JSPS and Gatsby Foundation.


1.         Stuart GJ, and Häusser M. Dendritic coincidence detection of EPSPs and action potentials. Nature Neuroscience 4: 63-71, 2001.



We thank Alanna Watt, Arnd Roth, Kazuo Kitamura, Mickey London, Niraj Desai and Julian Jack for help and useful discussions, and Latha Ramakrishnan for assistance with histology and Neurolucida reconstructions.