Stress activates the HPA axis resulting in the elevated secretion of glucocorticoids, catecholamines, enkephalins and other neuromodulators, which directly affect the hippocampus and amygdala. The magnitude of the influence of stress neuromodulators (variable s) on the hippocampus is a function of stress neuromodulators denoted by h(s), and the stress influences on the amygdala is denoted by g(s). The output from the amygdala (variable m) is a crucial component of the stress-induced modulation of hippocampal plasticity. The interaction between influences from the amygdala (m) and stress neuromodulators directly on the hippocampus (h(s)) is a function of both m and h(s) and is denoted by f(m,h(s)). Thus, the model illustrates that when there is an experimentally-induced reduction of amygdala input to the hippocampus (as a result of amygdala damage or inactivation, m=0), plasticity in the hippocampus is intact under stress conditions (upper right). On the other hand, with intact amygdalar input in response to stress, plasticity in the hippocampus is disturbed (i.e., impaired LTP and enhanced LTD; lower right). The green circles on the matrices represent synapses with normal capacity to generate plasticity (e.g., normal LTP) thereby accommodating normal hippocampal-dependent memory. The red circles represent synapses following stress with altered plasticity property (e.g., impaired LTP and enhanced LTD), which impairs subsequent hippocampal-dependent memory. The model proposes that the function f(m,h(s)) denotes the influence of stress on the hippocampus via two pathways (direct neurochemical influence and through the amygdala influence), and the conjunction of both inputs (m and h(s)) is required for plasticity is the hippocampus to be disrupted. The model predicts that stress effects on the hippocampus can be prevented by reducing the amygdalar output (upper part of the figure) to the hippocampus. Conversely, the model also predicts that stress effects on the hippocampus can be exacerbated by increasing the amygdalar output to the hippocampus. From Kim JJ and Diamond DM (2002). The stressed hippocampus, synaptic plasticity and lost memories. Nature Reviews Neuroscience 3: 453-462.