The Role Of Mediodorsal Thalamus-medial Prefrontal Cortex Pathway In Self-determined Decision-making Task

In the process of decision-making,decision-makers need to correctly evaluate the relationship between the cost and the benefit,and adjust their behaviors in order to make optional and wise decisions.Studies have shown that the prefrontal cortex(PFC),the only neocortical area that receives projections from the mediodorsal thalamus(MD),plays a key role in decision-making.However,the functional significance of the MD-PFC pathway in decision-making is unknown.Here,we established a decision-making paradigm in rats,in which the time of nose poking in a hole was used as a behavioral "cost" and the amount of water reward as a "benefit".In this task,the duration of nose poking in the hole was determined by the animals themselves.The longer the nose-poking duration was,the more water reward the rat was given.The benefits is linearly proportional to cost.After trained,the rats demonstrated normal distributions of nose poking time.Our results showed that,inactivation of the mPFC or the MD by local infusion of the GABAa receptor agonist muscimol severely impaired the task performance,that is,the rats were unwilling to pay a higher "cost" and the nose poking duration was significantly shortened.When the MD-mPFC pathway was stimulated by optogenetics,the rats paid more "costs" and got more water reward,whereas when the MD-mPFC pathway was inhibited optogenetically,the rats paid less "costs" and got less water reward.Electrophysiological recording showed that there existed mPFC neurons encoding the decision-making task events,and the task-related activities of such neurons were up-or down-regulated upon optogenetically stimulating or suppressing the MD-mPFC pathway.These results suggest that both mPFC and MD are required for the self-determined decision-making,and the MD-mPFC pathway plays a key role in regulating the firing of mPFC neurons related to the decision-making.This work deepens our understanding of the circuit mechanism underlying decision-making.