, 227 (1982); P. R. Montague and T. J.
, 1 (1994).
27. G. J. Stuart, H. U. Dodt, B. Sakmann,
, 511 (1993).
28. J. C. Magee, R. B. Avery, B. R. Christie, D. Johnston,
, 3460 (1996).
29. N. Lasser-Ross, H. Miyakawa, V. Lev-Ram, S. R.
Young, W. N. Ross,
30. We thank B. Christie, C. Colbert, and P. R. Montague
for helpful discussions and comments on the manu-
script. Supported by NIH grants NS09482 (J.C.M.)
and NS11535, MH44754, and MH48432 (D.J.).
17 September 1996; accepted 5 November 1996
Regulation of Synaptic Efficacy by Coincidence
of Postsynaptic APs and EPSPs
Henry Markram,* Joachim Lu
¨ bke, Michael Frotscher,
Activity-driven modifications in synaptic connections between neurons in the neocortex
may occur during development and learning. In dual whole-cell voltage recordings from
pyramidal neurons, the coincidence of postsynaptic action potentials (APs) and unitary
excitatory postsynaptic potentials (EPSPs) was found to induce changes in EPSPs. Their
average amplitudes were differentially up- or down-regulated, depending on the precise
timing of postsynaptic APs relative to EPSPs. These observations suggest that APs
propagating back into dendrites serve to modify single active synaptic connections,
depending on the pattern of electrical activity in the pre- and postsynaptic neurons.
epetitive activation of neuronal circuits
can induce long
term changes in subse
quent responses generated by synapses in
many regions of the brain, and such plastic
ity of synaptic connections is regarded as a
cellular basis for developmental and learn
related changes in the central nervous
). The actual triggers for synap
tic modifications between two neurons are,
however, unclear (
). Postsynaptic APs are
initiated in the axon and then propagate
back into the dendritic arbor of neocortical
pyramidal neurons (
), evoking an activity
dependent dendritic Ca
could be a signal to induce modifications at
the dendritic synapses that were active
around the time of AP initiation. To test
this hypothesis, we made dual whole
voltage recordings from neighboring, thick,
tufted pyramidal neurons in layer 5 of the
neocortex (Fig. 1A) for which the dendritic
locations of synaptic contacts were known
), and we investigated whether the
postsynaptic AP could induce changes in
unitary EPSP amplitudes.
When depolarizing current was injected
only into the cell body of a presynaptic
neuron to evoke a burst of APs, the result
frequency train of subthreshold
unitary EPSPs (Fig. 1B) failed to trigger
changes in the average EPSP amplitudes
(Fig. 1D), possibly because EPSP ampli
tudes decreased rapidly and a sufficiently
large postsynaptic depolarization was not
). When the postsynaptic neuron
was further depolarized by current injection
to produce a burst of APs during the EPSPs,