Lateralization of medial prefrontal cortex in stress response

Abstract

Since the 1960s’, it is reported that there is the lateralization of two anatomically homologous regions of the brain. Detailed understanding of these phenomena has yet to be discovered and only a few molecular targets have been proposed. Using the chronic social defeat stress model, social preference was diversified into two groups: susceptible and resilient. Lateralization of activity was proved by the neural firing rate and fosb expression in the left medial prefrontal cortex (mPFC), which also showed a significant correlation with social preference. Optogenetic stimulation of excitatory neurons in the left mPFC preferentially increases sociability. Otherwise, firing rate increases in the right mPFC of mice doesn’t make any difference. Optogenetic inhibition of excitatory neuronal in the left mPFC firing makes resilient mice to socially avoidant, vice versa. When the right mPFC is removed by electrolytic lesions before administering stress, mice act as if they had not received stress. . There are genes which change specifically in either the left or right mPFC, such as mef2c, drd1a and dopamine signaling pathway related molecules. MEF2C differentially lateralized in the brains of mice in the susceptible and resilient groups. Bioinformatics analysis showed that VEGF was an important upstream regulator. We observed that VEGF increases only in the right mPFC of the resilient group. VEGF infusion increases social preference only when infused into the right mPFC. So far evidence has been gathered and connects how social defeat stress can make mice respond differently through lateralized working mechanisms. For the susceptible phenotype, dendritic length modification by MEF2C causes a decrease of neural firing, whereas for the susceptible group, right side VEGF secretion increases sociability. Whether right side VEGF acts on the left side by inhibiting the inhibition of neural firing or increasing neural firing remains to be found. More cell type specific connect...