Physiological Basis of SBML Model. This figure describes the relationships between cortisol synthesis by the HPA axis and cortisol binding to hippocampal MR receptors with respect to synaptic firing at CA1 hippocampal neurons. Hippocampal atrophy is related to the numbers of neurons within the CA1 region, further defined by the branching of neurons therein. Ageing-related changes are shown chiefly as cell loss from hypothalamic hippocampal and pituitary tissues, along with a decline in the synthesis and availability of trophic factors. Stress associated changes are shown by the dashed arrow to GR receptors whereby elevated cortisol induces the expression of GR receptors, which are associated with CA1 neuronal synaptic inhibition. The combined effects of aging and stress may decrease hippocampal activity- defined as a combination of synaptic excitation and inhibition, and increase hippocampal atrophy.