Nuclear calcium signals during L-LTP induction do not predict the degree of synaptic potentiation

The magnitude and/or duration of nuclear Ca2+-transients has been shown to dose-dependently modulate gene transcription upon neuronal activation. This is an attractive model for synapse-to-nucleus communication. In order to encode synaptic information, these nuclear Ca2+-transients have to be correlated with changes in synaptic strength rather than changes in gene expression patterns. In this study, we analysed nuclear Ca2+ signals during L-LTP induction. Using a combined approach of fEPSP recordings and two-photon imaging, these Ca2+ signals were correlated with different degrees of synaptic potentiation in CA1 hippocampal slices. To refine our analysis on the single-cell level, we developed a new approach called single-cell-excitability-probing (SCEP) to assay the plasticity outcome of individual cells by optical means. The degrees of synaptic potentiation we observed could be categorized into transcription independent, transcription-dependent and reduced transcription-dependent. There is no consistent dose-dependent relationship between these different degrees of synaptic potentiation and the magnitude, the decay time and the area under the curve of nuclear Ca2+-transients during L-LTP induction. This indicates that nuclear Ca2+-transients during induction are unsuited to grade the degree of plasticity in an analogue manner. We propose a role for nuclear Ca2+ as a digital on/off switch for activating transcription.