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What are the typical calcium levels reached in single postsynaptic spines following activation of NMDA receptors by an EPSP or backpropagating spike? Everyone seems to refer to that one Neuron paper (Sabatini et al. 2002) which reports experimental estimates of around 1 uM following single synaptic stimulation in CA1 neuron spines. However, most computational papers on LTP (even biophysically detailed models) work with much lower values for Ca2+ transients that do not seem to have concrete experimental support. I am trying to put together a realistic model for hippocampal spine calcium signaling, and would really appreciate it if anyone can point out other relevant experimental papers that provide estimates for spine calcium transients.

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An earlier source for an estimate of ${[Ca]_{i}}^{+2}$ in spines comes from hippocampal slices of P13-P19 rats (Majewska et al. 2000). The resting ${[Ca]_{i}}^{+2}$ in this paper was ~80 nM and a back-propagating action potential (AP) elicited a response up to ~250 nM (change of ~170 nM). They included $F_{min}$ and $F_{max}$, the minimum and maximum fluorescence signal from a single AP, as parameters in the equation they used to estimate ${[Ca]_{i}}^{+2}$. This paper may be where the models you mention got their numbers from.

The resting ${[Ca]_{i}}^{+2}$ estimated in Sabatini et al. (2002), where they also used rat hippocampal slices from P14-P20, matches that found in Majewska et al. as it was ~70 nM. For the estimation of the evoked change in ${[Ca]_{i}}^{+2}$ after a single AP they used the maximum fluorescence increase from trains of action potentials at 62.5 Hz and 83.3 Hz as a parameter in their estimator equation, assuming that the calcium indicator was fully saturated at those stimulation frequencies. Their estimate for the change in ${[Ca]_{i}}^{+2}$ per AP was about 530 nM. They then reasoned that the buffering properties of the calcium indicator itself could reduce the change in ${[Ca]_{i}}^{+2}$. Thus they loaded several different calcium indicators with different affinities and at different concentrations, in order to manipulate the $\kappa_b$, the buffer capacity, of the calcium indicator. They observed a very strong linear relationship between $\kappa _b$ and the change in ${[Ca]_{i}}^{+2}$. By extrapolating from a linear fit on these data, they concluded that in the case where there was no calcium indicator in the cell —i.e. when $\kappa _b = 0$— the change in ${[Ca]_{i}}^{+2}$ per AP would be approximately 1 $\mu$M.

So the difference between these studies is that in Majewska et al. they used the maximum observed fluorescence of the calcium indicator in their data after single APs, whereas in Sabatini et al. they attempted to saturate the calcium indicator with high-frequency trains of APs. Furthermore, in Sabatini et al. they attempted to account for the buffering capacity of the calcium indicator itself, thus arriving at a more unbiased estimate.

Reassuringly, later work from the Yuste lab (the same lab as in the Majewska et al. study) could replicate the results of Sabatini et al. when they used similar methodology (Cornelisse et al. 2007). Their estimate for $\Delta{[Ca]_{i}}^{+2}$ for a single AP was also ~1 $\mu$M.

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