Figure 4. Ca²⁺ release from ER robustly enhances the spine Ca²⁺ signal and facilitates LTD induction at low input rates.

A, time course of Ca²⁺ evoked by repeated synaptic input at 1 Hz in the model ER⁻ spine (black) and an equivalent ER⁺ spine with 10–50 IP₃ receptors. ΔCa_EPSP = 0.2 μM in the ER⁻ spine. B, the corresponding time dependence of Ca²⁺-bound calmodulin (CaM) in the ER⁻/ER⁺ spine head. Total CaM concentration = 50 μM. C, change in the synaptic weight variable, w, driven by the activated CaM during a 1 Hz input train applied for 15 min (900 spikes). For this specific instantiation of the model, the plasticity threshold θ_D has been set to 2 μM, such that no LTD is induced in the absence of ER contribution, and LTD induction is facilitated with increasing flux through IP₃Rs. D, the amplitude of CaM response to synaptic inputs in the 0.1–5 Hz range is compared between the ER⁻ spine (black) and equivalent ER⁺ spine with 10–50 IP₃ receptors (coloured curves). E, change in the weight variable w at the end of 900 spikes in the ER⁻ (black) and ER⁺ spines (coloured curves), corresponding to D. θ_D is set to give no LTD in the ER⁻ spine for frequencies ≲ 1 Hz. F, the differential CaM response profile in an ER⁺ spine with 30 IP₃Rs relative to the ER⁻ spine for different choices of ΔCa_EPSP (i.e. NMDAR conductance). G, differential LTD induction, ΔΔw, in an ER⁺ spine with 30 IP₃Rs relative to an ER⁻ spine for different choices of ΔCa_EPSP. H, change in maximum CaM activation due to the presence of ER (30 IP₃Rs) as a function of the NMDAR conductance and a range of low induction frequencies. I, difference in synaptic weight change between the ER⁺ and ER⁻ spine, as a function of the NMDAR conductance and induction frequency. Lighter colours indicate enhanced LTD response in the presence of ICCR. [Colour figure can be viewed at wileyonlinelibrary.com]