Overview of modeling platform. The modeling platform consists of two components, a receptor competition model (left column) and a biophysical neuronal network model (center column). The receptor competition model calculates the activation of receptors for neuromodulators (M1, α7, α4β2 receptors for acetylcholine; D1, D4 receptors for dopamine; 5-HT1A, 5-HT2A, 5-HT3 receptors for serotonin; α2A receptors for norepinephrine) for the region of the brain represented by the neuronal network model. The receptor activations are used to adjust modulate synaptic and membrane currents in the network model. The output of the network model simulates a burst of pyramidal cell activity as a measure of working memory (right column). The platform is initially calibrated to generate an average working memory span of over 9 sec (top row), and a disease pathology such as loss of neurons and synapses reduces the working memory span (middle row). Changes in the receptor activations, such as increased cholinergic tone change the working memory span (bottom row) to reduce the symptoms.