Blockade Of ErbB4 Receptors In The Dorsolateral Prefrontal Cortex Impaired Spatial Working Memory In Rhesus Monkey

Schizophrenia is a serious mental illness,affecting nearly 1% of the world population,which brings huge burden to patients,their families and our society.Unfortunately,there is less effective treatment for it yet.Studies have shown that schizophrenia susceptibility genes NRG1 and ErbB4 are involved in maintaining working memory in rodents.However,it is unclear whether the NRG1/ErbB4 system also plays a key role in working memory of non-human primates.In this work,we trained two rhesus monkeys to master a spatial delayed-response task(SDR)and locally injected AG1478,the ErbB4 receptors antagonist into 46 D region of the dorsolateral prefrontal cortex to test its effects on the SDR performance of monkeys.We found that ErbB4 receptors in 46 D region was blocked by local injection of AG1478,and the SDR performance of monkeys were significantly impaired,while solvent DMSO injected in the same region did not make any difference.Injection of AG1478 into 46 V region of the prefrontal cortex did not affect the SDR performance of monkeys either,indicating the drug effects had a brain region specificity.Besides,local injection of AG1478 into 46 D region caused huge changes in task-focused and mental state-related behaviors in monkeys.Our results indicated that blocking the function of ErbB4 receptors in 46 D region of the dorsolateral prefrontal cortex leaded to impaired spatial working memory and behavioral changes in monkeys,which is similar to the symptoms appeared in schizophrene.This work may offer more insights in further studies of the biological basis of schizophrenia and the development of new strategies for treating schizophrenia.