The Study Of The Anterior Cingulate Cortex Based On Optical Detection And Manipulation Methods In The Behavior Mice

The reward is the motivation of humans and animals to dynamically adjust rewardseeking behaviors.The reward value often decreases with its repeat consumption in a short time.Reward devaluation is an effective balancing mechanism for appropriate reward intake,and excessive reward devaluation is speculated to be the cause of anhedonia in depression.However,the neural circuitry mechanisms of reward devaluation and depression are not well understood.Most previous studies focused on primates,and there are limited ways to detect and manipulate neurons.As optical detection and manipulation methods for neuronal activity are widely used in neuroscience,these methods can be used to further explore the neural mechanisms of reward devaluation and depression in mice.The anterior cingulate cortex(ACC)is thought to be involved in reward processes and depression,but the exact neural mechanisms are unclear.Abnormal reward devaluation is associated with depression in the chronic restraint stress(CRS)mice confirmed by the experiment of reward devaluation.By fiber photometry and in vivo calcium imaging in the ACC,it revealed that the ACC Ca MKII neurons encoded the reward devaluation.Functional impairment and chemogenetic manipulation of the ACC Ca MKII neurons suggested that the ACC regulated the process of reward devaluation and depressive behavior.Furthermore,the basolateral amygdala(BLA)-projecting ACC neurons were identified to control reward devaluation and affect depressive behaviors through neural circuit tracing,single-cell whole-brain three-dimensional spatial reconstruction technology,and AAV-retro labeling strategy.This study reveals that the basolateral amygdala-projecting ACC neurons encode reward devaluation and can be the potential mechanism of depressive behavior,which provides a potential mechanism and treatment of depression.To further explore the precise encoding of reward in the ACC,a GRIN lens-based UCLA miniscope was used to image the ACC Ca MKII neurons.The ACC Ca MKII neurons can encode valence for preference and aversive stimuli in the water pumping experiment and electric shock experiment.It was found that the ACC Ca MKII neurons could specifically encode valence of the outcomes during the learning process in the Go/no go odor training experiment;It also revealed that there were eight types of neurons encoding value size;For the reward or punishment signal processing,they can encode prediction,outcome or both in the time course.Finally,we reveal the function of the ACC neurons to encode the valence of reward and punishment signal processing.These calcium imaging results based on the miniscope showed that ACC Ca MKII neurons were the source of valence,which would benefit the application of calcium imaging in the deep brain and the study of ACC.To study the causality between neuron activity and behavior by monitoring and manipulating the neuronal activity,an all-fiber recording and manipulation system based on multi-branch fiber bundles has been developed for dual-color recording and optogenetic manipulation of neuronal calcium activity or neurotransmitter activity in freely moving animals.It demonstrated successful dual-color recording of neuronal Ca2+signals and DA dynamics in the NAc upon delivering an unexpected reward and the simultaneous optogenetic activating at dopaminergic terminals in the same location,which showed a different pattern.The system is an effective supplement to the current optical methods based on fiber optics and provides an effective detection method for further observing the activity of different types of neurons and monitoring the feedback effect caused by the intervention of optogenetics in neural circuits.It is meaningful for the causal study of neural circuits and neurological diseases.Understanding the function of the brain and the treatment of brain diseases by using optical methods is one of the most challenging scientific frontiers.This dissertation explored the function and neural circuitry mechanisms of ACC in depression.To study the function of ACC in reward encoding,a GRIN lens-based miniscope was used.In addition,an all-fiber recording and manipulation system was developed to monitor and manipulate neuronal activity.These optical fiber-based optical methods provide effective technical methods for the study of brain function and provide technical support for further exploration of the mechanism and treatment of brain-related diseases.