OptogeneticStimulation of the Anterior Cingulate Cortex Ameliorates Autistic-Like Behaviors in Rats Induced by Neonatal Isolation, Caudate Putamen as a Site for Alteration

Epigenetic agents, such as neonatal isolation during neurodevelopmental period of life, can change various regions of the brain. It may further induce psychological disorders such as autistic-like phenomena. This study indicated the role of chronic increased anterior cingulate cortex (ACC) output on alteration of caudate putamen (CPu) as a main behavior regulator region of the brain in adult maternal deprived (MD) rats. For making an animal model, neonates were isolated from their mothers in postnatal days (PND 1-10, 3h/day). Subsequently, they bilaterally received pLenti-CaMKIIa-hChR2 (H134R)-mCherry-WPRE virus in ACC area via stereotaxic surgery in PND50. After 22 days, these regions were exposed to blue laser (473nm) for six consecutive days (15min/day). Then, behavioral deficits were tested and were compared with control group in the following day. Animals were immediately killed and their brains were prepared for tissue processing. Results showed that neonatal isolation induces autistic-like behaviors and leads to overexpression of NMDAR1 and Nox2-gp91(phox) proteins and elevation of catalase activity in the CPu regions of the adult offspring compared with control group. Chronic optogenetic stimulation of ACC neurons containing (ChR2+) led to significant reduction in the appearance of stereotypical behavior and alien-phobia in MD rats. The amount of NMDAR1 and Nox2-gp91(phox) expression and the catalase activity in CPu were reduced after this treatment. Therefore, autistic-like behavior seems to be related with elevation of NMDAR1 and Nox2-gp91(phox) protein levels that enhance the effect of glutamatergic projection on CPu regions. Optogenetic treatment also could ameliorate behavioral deficits by modulating these protein densities.