Analysis of neural circuit alterations caused by chronic social stress

Stress caused by aversive and psychological stimuli induces sustained emotional and cognitive abnormalities and precipitates the onset and relapse of symptoms in psychiatric illnesses, such as depression. We have demonstrated that chronic social stress causes dendritic atrophy of pyramidal neurons in the medial prefrontal cortex (mPFC) only in mice susceptible to chronic social stress, whereas acute social stress leads to dendritic growth of these neurons concomitant with suppression of behavioral changes. However, it remains unknown how stress-induced dendritic remodeling of mPFC pyramidal neurons affects neural circuits associated with depressive behaviors. Here we utilized monosynaptic retrograde tracing with a G-deficient rabies viral vector to identify neural projections to the mPFC that can be anatomically altered by chronic social stress. A G-deficient rabies viral vector encoding a red fluorescent protein (RFP) was unilaterally infused into the mPFC to visualize neurons that directly input to the mPFC. Among 90 brain regions where RFP-positive cells were observed in mice subjected to chronic social stress, some particular regions showed a decrease or increase in RFP-positive cells. This finding suggests that chronic social stress anatomically alters neural projections to the mPFC, leading to sustained behavioral changes.