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Frequency-dependent changes in NMDAR-dependent synaptic plasticity

Arvind Kumar^1,2 and Mayank R. Mehta^3,4,5*

¹ Bernstein Center Freiburg, University of Freiburg, Freiburg, Germany
² Neurobiology and Biophysics, University of Freiburg, Freiburg, Germany
³ Department of Physics and Astronomy, University of California Los Angeles, Los Angeles, CA, USA
⁴ Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA
⁵ Department of Neurobiology, University of California Los Angeles, Los Angeles, CA, USA

The NMDAR-dependent synaptic plasticity is thought to mediate several forms of learning, and can be induced by spike trains containing a small number of spikes occurring with varying rates and timing, as well as with oscillations. We computed the influence of these variables on the plasticity induced at a single NMDAR containing synapse using a reduced model that was analytically tractable, and these findings were confirmed using detailed, multi-compartment model. In addition to explaining diverse experimental results about the rate and timing dependence of synaptic plasticity, the model made several novel and testable predictions. We found that there was a preferred frequency for inducing long-term potentiation (LTP) such that higher frequency stimuli induced lesser LTP, decreasing as 1/f when the number of spikes in the stimulus was kept fixed. Among other things, the preferred frequency for inducing LTP varied as a function of the distance of the synapse from the soma. In fact, same stimulation frequencies could induce LTP or long-term depression depending on the dendritic location of the synapse. Next, we found that rhythmic stimuli induced greater plasticity then irregular stimuli. Furthermore, brief bursts of spikes significantly expanded the timing dependence of plasticity. Finally, we found that in the ∼5–15-Hz frequency range both rate- and timing-dependent plasticity mechanisms work synergistically to render the synaptic plasticity most sensitive to spike timing. These findings provide computational evidence that oscillations can have a profound influence on the plasticity of an NMDAR-dependent synapse, and show a novel role for the dendritic morphology in this process.

Keywords: STDP, calcium dependent plasticity, NMDA synapses, oscillations, 1/f, LTP, LTD

Citation: Kumar A and Mehta MR (2011) Frequency-dependent changes in NMDAR-dependent synaptic plasticity. Front. Comput. Neurosci. 5:38. doi: 10.3389/fncom.2011.00038

Received: 04 March 2011; Accepted: 07 September 2011;
Published online: 29 September 2011.

Edited by:

Stefano Fusi, Columbia University, USA

Reviewed by:

Carmen Canavier, LSU Health Sciences Center, USA
Magnus Richardson, University of Warwick, UK
Sonia Gasparini, LSU Health Sciences Center, USA

Copyright: © 2011 Kumar and Mehta. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Mayank R. Mehta, Departments of Physics and Astronomy, Neurology, Neurobiology, Integrative Center for Learning and Memory, University of California at Los Angeles, Los Angeles, CA, USA. e-mail: mayankmehta@ucla.edu