Fig. 1: Modeling the role of postsynaptic calcium in LTP/LTD.

a A 3-D rendering of a neocortical column in the circuit model used in this study. Neuronal morphologies are colored according to their layer of origin (axons not shown). b Schematic of the main players and events contributing to LTP/LTD induction at excitatory synapses (bottom) between pyramidal neurons (top). Pre-synaptic vesicle release and subsequent post-synaptic depolarization results in calcium influx in dendritic spines via NMDARs and VDCCs. Calcium signaling activates independent biochemical pathways, leading to long-term changes in AMPAR conductance (postsynaptic expression mechanisms) and/or vesicle release probability (presynaptic expression mechanisms). c Calcium transients at a single synapse during repetitive firing of the presynaptic neuron at 10 Hz (upper three panels; Trial 1-3). Trial-to-trial variability is governed by the rapid depletion of the number of vesicles available for release and the resulting drop in success rate (bottom; data shown as mean ± STD, n = 10). d Calcium transients at a single synapse during repetitive firing of the postsynaptic neuron at 10 Hz. VDCCs respond with reliable calcium transients to postsynaptic spikes. e Calcium transients at a single synapse during repetitive pairing of the pre- and post-synaptic neuron at 10 Hz. Presynaptic spikes shortly preceding postsynaptic spikes (blue, +10 ms) cause nonlinear activation of the NMDARs and a large calcium influx. The inverse timing relationship (post before pre, red, −10 ms) results in an almost linear summation of NMDAR- and VDCC-mediated calcium transients.