Figure 1. Schematic of cortical model showing (A) neuronal network connectivity; (B) molecular interactions in pyramidal cells.

(A) Red rectangles represent populations of 5-compartment excitatory cells (largest rectangle represents soma, 3 apical-dendrite compartments point upward, basal dendrite compartment points downward; multiple compartments allow more realistic spatial/temporal integration of synaptic inputs); green circles represent fast-spiking interneurons; blue ellipses represent low-threshold firing interneurons. Lines (with arrows) indicate connections between the populations. E cells synapse with AMPAR/NMDARs; I cells synapse with GABA_AR / GABA_BRs. Filled circles represent GABA_AR / GABA_BRs. Open circles and rectangles represent AMPAR/NMDARs. (B) Schematic of chemical signaling in pyramidal cells showing fluxes (black arrows) and second- (and third-etc) messenger modulation (red back-beginning arrows). We distinguish membrane-associated ionotropic and metabotropic receptors and ion channels involved in reaction schemes in red. External events are represented by yellow lightning bolts – there is no extracellular diffusion; the only extracellular reaction is glutamate binding, unbinding and degradation on mGluR1 after an event. Ca²⁺ is shown redundantly in blue – note that there is only one Ca²⁺ pool for extracellular, 1 pool for cytoplasmic, and 1 pool for ER. (PLC: phospholipase C, DAg: diacyl-glycerol, cAMP: cyclic adenosine monophosphate; PIP₂: phosphatidylinositol 4,5-bisphosphate).