Questions about STDP as a General Model of Synaptic Plasticity

John Lisman,Nelson Spruston

doi:10.3389/fnsyn.2010.00140

Abstract

According to spike-timing-dependent plasticity (STDP), the timing of the Na+ spike relative to the EPSP determines whether LTP or LTD will occur. Here, we review our reservations about STDP. Most investigations of this process have been done under conditions in which the spike is evoked by postsynaptic current injection. Under more realistic conditions, in which the spike is evoked by the EPSP, the results do not generally support STDP. For instance, low-frequency stimulation of a group of synapses can cause LTD, not the LTP predicted by the pre-before-post sequence in STDP; this is true regardless of whether or not the EPSP is large enough to produce a Na+ spike. With stronger or more frequent stimulation, LTP can be induced by the same pre-before-post timing, but in this case block of Na+ spikes does not necessarily prevent LTP induction. Thus, Na+ spikes may facilitate LTP and/or LTD under some conditions, but they are not necessary, a finding consistent with their small size relative to the EPSP in many parts of pyramidal cell dendrites. The nature of the dendritic depolarizing events that control bidirectional plasticity is of central importance to understanding neural function. There are several candidates, including backpropagating action potentials, but also dendritic Ca2+ spikes, the AMPA receptor-mediated EPSP, and NMDA receptor-mediated EPSPs or spikes. These often appear to be more important than the Na+ spike in providing the depolarization necessary for plasticity. We thus feel that it is premature to accept STDP-like processes as the major determinant of LTP/LTD.

Highlights

Introduction by Chief Editor Mary BKennedy The Editors of the Special Issue on “Spike-Timing Dependent Plasticity,” Jesper Sjöström and Henry Markram, asked John Lisman and Nelson Spruston to summarize and elaborate on their 2005 commentary (Lisman, J., and Spruston, N. (2005)
We presented a critique of spike-timing-dependent plasticity (STDP), questioning whether it occurs under such natural conditions (Lisman and Spruston, 2005)
Question: Perhaps the spike is unimportant during synaptically induced LTP/LTD, but doesn’t the spike do the job in STDP protocols? Answer: The repetition rates typically used are so high that other types of dendritic events such as Ca2+ spikes may be inadvertently induced by summation of EPSPs, complicating the interpretation

Summary

Question

How is the critical source of the postsynaptic depolarization required for plasticity going to be determined? Answer: It’s a hard problem. Using a combination of factors related to the pre and postsynaptic membrane potentials (see Spruston and Cang, 2010), the model explains the dependence of LTP/LTD on stimulus frequency, postsynaptic bursting, and the synaptic depolarization. Future implementations of the model could seek to explain the dependence of synaptic plasticity on specific biophysical events, such as dendritic spikes and inhibition, in compartmental models of neurons with elaborate dendritic trees endowed with a variety of conductances. It will be of interest to see whether this class of model can explain why the phase of synaptic stimulation during theta frequency oscillations can determine whether LTP or LTD is induced (Huerta and Lisman, 1995; Hyman et al, 2003; Kwag and Paulsen, 2009)