Elucidation of mechanisms and pathophysiological significance of neural circuit formation and plasticity

Abstract

Neural circuits are mainly formed by genetic programs in early development but reorganized after birth under the influence of external factors. We have focused on social and environmental stress as an external factor and analyzed stress-induced changes in neural circuits and their functional significance. Long-term (chronic) stress attenuates dopaminergic function in the medial prefrontal cortex, leading to depressive-like behavior. Along with this behavioral change, long-term stress causes dendritic atrophy of pyramidal neurons in the medial prefrontal cortex. On the other hand, we found that short-term stress (acute) stress suppresses depressive-like behavior via dopamine response and dopamine D1 receptor signaling in the medial prefrontal cortex and induces dendritic hypertrophy of pyramidal neurons in a D1 receptor-dependent manner. Concomitantly, short-term stress increases the neural activity of the extended amygdala via dopamine D1 receptors in the medial prefrontal cortex. We have also revealed that rapid antidepressant effects of ketamine are mediated by neural circuits similar to those activated by short-term stress. In this presentation, I would like to introduce our recent findings and future directions on neural circuit plasticity in stress and depression.