Learning rules for spike timing-dependent plasticity depend on dendritic synapse location




Letzkus, Johannes
Kampa, Bjoern
Stuart, Gregory J

Journal Title

Journal ISSN

Volume Title


Society for Neuroscience


Previous studies focusing on the temporal rules governing changes in synaptic strength during spike timing-dependent synaptic plasticity (STDP) have paid little attention to the fact that synaptic inputs are distributed across complex dendritic trees. During STDP, propagation of action potentials (APs) back to the site of synaptic input is thought to trigger plasticity. However, in pyramidal neurons, backpropagation of single APs is decremental, whereas high-frequency bursts lead to generation of distal dendritic calcium spikes. This raises the question whether STDP learning rules depend on synapse location and firing mode. Here, we investigate this issue at synapses between layer 2/3 and layer 5 pyramidal neurons in somatosensory cortex. We find that low-frequency pairing of single APs at positive times leads to a distance-dependent shift to long-term depression (LTD) at distal inputs. At proximal sites, this LTD could be converted to long-term potentiation (LTP) by dendritic depolarizations suprathreshold for BAC-firing or by high-frequency AP bursts. During AP bursts, we observed a progressive, distance-dependent shift in the timing requirements for induction of LTP and LTD, such that distal synapses display novel timing rules: they potentiate when inputs are activated after burst onset (negative timing) but depress when activated before burst onset (positive timing). These findings could be explained by distance-dependent differences in the underlying dendritic voltage waveforms driving NMDA receptor activation during STDP induction. Our results suggest that synapse location within the dendritic tree is a crucial determinant of STDP, and that synapses undergo plasticity according to local rather than global learning rules.



Keywords: n methyl dextro aspartic acid; action potential; animal cell; animal experiment; article; calcium cell level; cell membrane depolarization; controlled study; dendritic cell; learning; long term depression; nerve cell plasticity; nonhuman; priority journal Backpropagating action potential; Burst; Calcium electrogenesis; Dendrite; NMDA receptor; Spike timing; Synaptic plasticity



Journal of Neuroscience


Journal article

Book Title

Entity type

Access Statement

License Rights



Restricted until