The hippocampus and the amygdala are essential components of the neural circuitry mediating stress responses. The hippocampus, which provides negative feedback regulation of the stress response, is particularly vulnerable to degenerative changes caused by chronic stress. Unlike the hippocampus, relatively little is known about how stress affects the amygdala and the nature of its role in the stress response. Hence, we examined the effects of two different models of chronic stress on hippocampal and amygdaloid neuronal morphology in rats. In agreement with previous reports, chronic immobilization stress (CIS) induced dendritic atrophy and debranching in CA3 pyramidal neurons of the hippocampus. In striking contrast, pyramidal and stellate neurons in the basolateral complex of the amygdala exhibited enhanced dendritic arborization in response to the same CIS. Chronic unpredictable stress (CUS), however, had little effect on CA3 pyramidal neurons and induced atrophy only in BLA bipolar neurons. These results indicate that chronic stress can cause contrasting patterns of dendritic remodeling in neurons of the amygdala and hippocampus. Moreover, CIS, but not CUS, reduced open-arm activity in the elevated plus-maze. These findings raise the possibility that certain forms of chronic stress, by affecting specific neuronal elements in the amygdala, may lead to behavioral manifestations of enhanced emotionality. Thus, stress-induced structural plasticity in amygdala neurons may provide a candidate cellular substrate for affective disorders triggered by chronic stress.

Emotionally significant experiences tend to be well remembered, and the amygdala has a pivotal role in this process. But the efficient encoding of emotional memories can become maladaptive - severe stress often turns them into a source of chronic anxiety. Here, we review studies that have identified neural correlates of stress-induced modulation of amygdala structure and function - from cellular mechanisms to their behavioural consequences. The unique features of stress-induced plasticity in the amygdala, in association with changes in other brain regions, could have long-term consequences for cognitive performance and pathological anxiety exhibited in people with affective disorders.

Fragile X syndrome (FXS) is the most common form of heritable mental retardation and the leading identified cause of autism. FXS is caused by transcriptional silencing of the FMR1 gene that encodes the fragile X mental retardation protein (FMRP), but the pathogenesis of the disease is unknown. According to one proposal, many psychiatric and neurological symptoms of FXS result from unchecked activation of mGluR5, a metabotropic glutamate receptor. To test this idea we generated Fmr1 mutant mice with a 50% reduction in mGluR5 expression and studied a range of phenotypes with relevance to the human disorder. Our results demonstrate that mGluR5 contributes significantly to the pathogenesis of the disease, a finding that has significant therapeutic implications for fragile X and related developmental disorders.