Copyright © 2015 David Parker.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The relevance of neuronal and synaptic variability remains unclear. Cellular and synaptic plasticity and neuromodulation are also variable.This could reflect state-dependent effects caused by the variable initial cellular or synaptic properties or direct variability in plasticity-inducingmechanisms.This study has examined state-dependent influences on synaptic plasticity at connections between excitatory interneurons (EIN) andmotor neurons in the lamprey spinal cord. State-dependent effects were examined by correlating initial synaptic properties with the substance P-mediated plasticity of low frequency-evoked EPSPs and the reduction of the EPSP depression over spike trains (metaplasticity).The low frequency EPSP potentiation reflected an interaction between the potentiation of NMDA responses and the release probability.The release probability introduced a variable state-dependent subtractive influence on the postsynaptic NMDA-dependent potentiation.Themetaplasticity was also state-dependent: it was greater at connections with smaller available vesicle pools and high initial release probabilities.This was supported by the significant reduction in the number of connections showing metaplasticity when the release probability was reduced by high Mg2+ Ringer. Initial synaptic properties thus introduce state-dependent influences that affect the potential for plasticity. Understanding these conditions will be as important as understanding the subsequent changes. 1
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