The Role Of Excitatory Neurons In The Anterior Cingulate Cortex In Cognitive Flexibility

Cognitive flexibility refers to the ability of individuals to adjust their behavior according to the changing environment,and is one of the core components of higher cognitive functions.The living environment throughout their life is so complex and changeable that healthy individuals need to adjust their behaviors in real time for better adaption to the environments.Many studies have also found that deficits in cognitive flexibility is one of the symptoms of many mental disorders.Therefore,understanding the neural mechanisms underlying cognitive flexibility is very important.Previous studies have indicated that the striatum,anterior cingulate cortex(ACC),insula and other brain regions are closely related to cognitive flexibility.The ACC plays an important role in both emotion and cognition control.However,most of the existing studies indirectly speculated the role of the ACC in cognitive flexibility through the behavioral changes caused by changing the activity of neurons in the ACC,and no consistent conclusions have been reached,so this research aims to explore the role of ACC excitatory neurons in cognitive flexibility from a more direct perspective.In this study,to assess cognitive flexibility in mice,we used visual discrimination reversal learning task.With the help of fiber Photometry technology and chemical genetic technology,our research attempt to elucidate the role of ACC excitatory neurons in cognitive flexibility.The experimental results recorded by fiber photometry showed the activity of ACC excitatory neurons increased significantly after mice touch screen during the correct trial in the medium phase of reversal learning stage.The activity of ACC excitatory neurons increased significantly after the last exit from the food trough during the discrimination learning stage and the reversal learning stage.The results of chemogenetic experiments showed that inhibition of ACC excitatory neurons in the early,medium and late phases of reversal learning stage had no effects on the cognitive flexibility which manifests as normal reverse learning.In conclusion,these results suggest that ACC excitatory neurons may play a significant role in cognitive flexibility because their activity increased significantly in the medium phase of reversal learning stage,which may be related to the ability of rule/information updating.Although chemogenetic experiments have not verified the above conclusion due to the possible influence of factors such as insufficient time to start inhibition and limited inhibition days,further exploration is needed in the future.Taken together,our study preliminarily demonstrated the important role of ACC excitatory neurons in cognitive flexibility,but a more specific neural mechanism remains to be further examined in future research.