strengthens the hypothesis that SSRIs act through neurogenesis to decrease the symptoms of depression. Some neuroscientists have expressed skepticism that neurogenesis is functionally significant, given that a tiny number of nascent neurons are actually integrated into existing neural circuitry. However, a recent study used the irradiation of nascent hippocampal neurons in non-human primates (NHP) to demonstrate that neurogenesis is required for antidepressant efficacy. Adult-born neurons appear to have a role in the regulation of stress. Studies have linked neurogenesis to the beneficial actions of specific antidepressants, suggesting a connection between decreased hippocampal neurogenesis and depression. In a pioneer study, scientists demonstrated that the behavioral benefits of antidepressant administration in mice is reversed when neurogenesis is prevented with x-irradiation techniques. In fact, newborn neurons are more excitable than older neurons due to a differential expression of GABA receptors. A plausible model, therefore, is that these neurons augment the role of the hippocampus in the negative feedback mechanism of the HPA-axis (physiological stress) and perhaps in inhibiting the amygdala (the region of brain responsible for fearful responses to stimuli). Indeed, suppression of adult neurogenesis can lead to an increased HPA-axis stress response in mildly stressful situations. This is consistent with numerous findings linking stress-relieving activities (learning, exposure to a new yet benign environment, and exercise) to increased levels of neurogenesis, as well as the observation that animals exposed to physiological stress (cortisol) or psychological stress (e.g. isolation) show markedly decreased levels of newborn neurons. Under chronic stress conditions, the elevation of newborn neurons by antidepressants improves the hippocampal-dependent control on the stress response; without newborn neurons, antidepressants are unable to restore the regulation of the stress response and recovery becomes impossible. Some studies have hypothesized that learning and memory are linked to depression, and that neurogenesis may promote neuroplasticity. One study proposes that mood may be regulated, at a base level, by plasticity, and thus not chemistry. Accordingly, the effects of antidepressant treatment would only be secondary to change in plasticity. However another study has demonstrated an interaction between antidepressants and plasticity; the antidepressant fluoxetine has been shown to restore plasticity in the adult rat brain. The results of this study imply that instead of being secondary to changes in plasticity, antidepressant therapy could promote it. Effects of sleep reduction One study has linked lack of sleep to a reduction in rodent hippocampal neurogenesis. The proposed mechanism for the observed decrease was