Lateral Habenula As A Trigger To Influence Aversion And Reward Behaviors In Mice

Organisms are instinctively motivate to survive by seeking profits and avoiding injury.The reward and aversion systems in the limbic forebrain and midbrain play a key role in shaping this motivational behavior in animals.Reward can induce pleasurable feelings and generate approach and trend behaviors,which eventually contribute to behavioral reinforcement,and arouse the goal-oriented motivation behavior response in the organisms,formed a positive reinforcement effect;inversely,aversive stimuli trigger negative emotions such as fear,dislike and disgust in animals,which further result in avoidance behavior and reduce the likelihood of an associated behavior being expressed,developed a negative reinforcement effect.The lateral habenula and ventral tegmental area,which serve,respectively,as the aversion and reward centers of the brain,are intimately connected to each other,reacting as an integral unit to various aversion and reward stimuli.This study investigated whether single neurons in the lateral habenula and ventral tegmental area can respond to both aversion and reward stimuli,further,whether they converge the two different types of information.In this study,optogenetic combined with multi-channel electrophysiological techniques were used to record the discharge of neurons in the lateral habenula and ventral tegmental area for further identifying the LHb glutamate neurons,as well as respectively analyzing the response of individual neurons to reward and aversive stimulus in transgenic mice.Then,combined with optogenetics,behavioral tests were used to assess the aversion or reward behaviors of mice in context of the glutamatergic neurons in the lateral habenula or their terminals in the ventral tegmental area were respectively excited or inhibited by light stimulation.Our findings demonstrated that 75% and 55% of single neurons,respectively,in the lateral habenula and ventral tegmental area are responded to both aversion and reward stimuli(convergent neurons),but their general response towards the two types of stimuli was opposite.Interestingly,77% of convergent neurons in the lateral habenula were aversion-activated,reward-inhibited neurons,consisting mainly of glutamatergic neurons(88%).In contrast,51% of convergent neurons in the ventral tegmental area were aversion-inhibited,reward-activated neurons,which were significantly inhibited by the activation of glutamatergic neurons in the lateral habenula.Furthermore,activation of glutamatergic neurons in the lateral habenula,as well as activation or inhibition their terminals in ventral tegmental area could induce aversive or reward behaviors in mice,however,inhibition of glutamatergic neurons in the lateral habenula failed to elicit reward behavior.These findings indicate that both glutamatergic convergent neurons in the lateral habenula and convergent neurons in the ventral tegmental area act to integrate reward and aversion information,playing a vital role in regulating reward and aversion behaviors.