Modeling of Spike Timing-Dependent Plasticity in the Presence of Complex Spike Protocols

Abstract

Spike timing-dependent plasticity (STDP) is a process in which changes in synaptic strength are determined by the relative timing of pre- and post-synaptic activity. STDP can result in either long term potentiation (LTP) or long term depression (LTD), and there is strong experimental evidence that these changes are driven by the postsynaptic Ca2+ concentration. Previously we examined a computational model of STDP that combines the chemical network model of Pi and Lisman (2008), with a model of Ca2+ dynamics that builds on the work of Shouval and coworkers (2002) to explain experimental studies of STDP in response to pre- and post-synaptic spike pair protocols (Carlson and Giordano, 2010). Wang et al. (2005) have also explored more complex spike timing protocols such as triplets and quadruplets, and the results in some cases cannot be explained simply in terms of the STDP behavior found in response to spike pairs. For example, a spike pair triplet can be viewed as a combination of one spike pair (spikes 1 and 2) followed by a second spike pair (spikes 2 and 3), and in some cases the resulting STDP is not the simple sum of that found for the two spike pairs. We have extended our model of STDP to explore the multi-spike cases studied by Wang et al. and careful examination of the Ca2+ dynamics shows how such “non-additivity” can occur. Carlson, K. D. and Giordano, N. J. (2010) to be published. Pi, H. J., and Lisman, J. E. (2008) J. Neurosci. 28: 13132–13138. Shouval, H. Z., Bear, M. F., and Cooper, L. N. (2002) Proc. Natl. Acad. Sci. USA 99: 10831–10836. Wang, H. X., Gerkin, R. C., Nauen, D. W., and Bi, G. Q. (2005) Nat. Neurosci. 8: 187–194.