Postsynaptic bursting is essential for 'Hebbian' induction of associative long-term potentiation at excitatory synapses in rat hippocampus

1. The biologically relevant rules of synaptic potentiation were investigat ed in hippocampal slices from adult rat by mimicking neuronal activity seen during learning behaviours. Synaptic efficacy was monitored in two separat e afferent pathways among the Schaffer collaterals during intracellular rec ording of CA1 pyramidal neurones. The effects of pairing presynaptic single spikes or bursts with postsynaptic single spikes or bursts, repeated at 5 Hz ('theta' frequency), were compared. 2. The pairing of ten single evoked excitatory synaptic events with ten pos tsynaptic single action potentials at 5 Hz, repeated twelve times, failed t o induce synaptic enhancement (EPSP amplitude 95% of baseline amplitude 20 min after pairing; n = 5). In contrast, pairing the same number of action p otentials, but clustered in bursts, induced robust synaptic potentiation (E PSP amplitude 163%; P < 0.01, Student's t test; n = 5). This potentiation w as input specific, long lasting (>1 h; n = 3) and its induction was blocked by an antagonist at NMDA receptors (20-50 mu M D(-)-2-amino-5-phosphonopen tanoic acid; EPSP amplitude 109%; n = 6). 3. Presynaptic bursting paired with postsynaptic single action potentials d id not induce input specific synaptic change (113% in the test input vs. 11 1% in the control; n = 8). In contrast, postsynaptic bursting when paired w ith presynaptic single action potentials was sufficient to induce synaptic potentiation when the presynaptic activity preceded the postsynaptic activi ty by 10 ms (150 vs. 84% in the control input; P < 0.01; n.= 10). 4. These results indicate that, under our conditions, postsynaptic bursting activity is necessary for associative synaptic potentiation at CA1 excitat ory synapses in adult hippocampus. The existence of a distinct postsynaptic signal for induction of synaptic change calls for refinement of the common interpretation of Hebb's rule, and is likely to have important implication s for our understanding of cortical network operation.