开题报告内容Content：（包括拟研究或解决的问题、采用的研究手段及文献综述，不少于2000字）Including objectives, methods adopted and literature review, no less than 2000 words
I. Background
The ability to flexibly alter behaviors according to the surroundings is of great importance. The control over decision making is predominantly goal-directed when the subject learns to perform an action and may eventually transfer to habitual behavior after repeated execution. 【1】 The actions under goal-directed control are sensitive to both outcome value and contingency, therefore, such actions are clearly driven by the goal (or outcome) and the relationship (or contingency) between the outcome and the action. 【1】 As these goal-directed actions are performed over time, the loss of behavioral flexibility can occur, leading to habitual behavior. 【2】 Habitual behavior is insensitive to changes in the value of the outcome and is insensitive to changes in the contingency between the action and the outcome. 【1】 Goal-directed control is in part regulated by the interaction between the medial prefrontal cortex (mPFC) and the posterior dorsomedial striatum (pDMS), while habitual behavior is under the control of the anterior dorsolateral striatum (aDLS), or putamen in humans, and motor cortical areas. 【3】
The formation of habits is the learning process of stimulus-response (S-R) despite the devaluation of reinforcement. 【7】 As with the learning of conditioned stimuli in habitual behavior, Pavlovian conditioning refers to the learning the association between a neutral stimuli and an unconditioned outcome. Thus, the previously neutral stimuli trigger conditioned response. 【7】 Thus, the brain regions involved in Pavlovian conditioning and stimulus-evoked responses may play a role in habitual behaviors. Drug-taking cues and contexts can be thought as drug-associated conditioned stimuli that promote maintenance of drug seeking and taking behavior (based on the Pavlovian instrumental transfer theory), thus, delineating habitual behavior. 【3】These reward-paired stimuli can act as reinforcers encoded by basolateral amygdala (BLA) through its projections to drug seeking actions. 【4】The postulation here is that the formation of habits, when the response is no longer sensitive to the outcome but rather is elicited by conditioned stimuli, may be encoded by BLA projections.
The amygdala CeN-DLS system plays an important role in Pavlovian conditioned orienting and the acquisition of food-reinforced habits. Two neural circuits by which amygdala influences habitual instrumental behavior have been previously identified: first, the central amygdala (CeN) projections directly to the substantia nigra pars compacta that sends dopaminergic projections the DLS, or second via glutamatergic BLA projections to the nucleus accumbens core (NAcbC). 【3】The BLA projections to the NAcbC influences the spiraling dopaminergic circuitry linking the core with the DLS. 【3】 Moreover, Murray and colleges found before cocaine seeking has become habitual, BLA is required to recruit aDLS control and then a functional shift occurs, allowing the CeN to maintain the control over habitual behavior. 【4】There is also possibility that drug withdrawal stress stimulates the stress systems in the amygdala to facilitate its coupling to DLS, thus influencing the development of S-R drug-seeking habits and lead to raised reward thresholds and long-term changes in hedonic state. 【3】 However, the role of BLA projections to nucleus accumbens shell (NAcbS) in goal-directed and habitual behaviors has not been studied yet. Thus, we will investigate the engagement of BLA to NAcbS projections to gain a better understanding of how BLA is involved in the expression of goal-directed action-outcome behaviors versus habitual S-R behavior.
Goal-directed control can be probed by outcome devaluation tests, more precisely, sensory-specific satiety, which focuses on the dysfunction in psychiatric disorder of addiction. Another test that is independent of the outcome value to measure the contingency sensitivity in goal-directed action is contingency degradation test, which detects the subjectrsquo;s ability to change its action in accordance with the alterations of the contingency. 【1】 The training of the same mouse on random ratio and random interval schedules can provide matched response rate and reinforcement rate across RR and RI responding. 【6】
The circuit mechanisms underlying the different behaviors can be detected by analyzing c-Fos combined with fluorescent imaging of retrograde tracers. C-Fos marked neurons are those that are activated after specific testing, while the projections are marked by the tracer. So, the amount of the overlap reflects which cells is both activated and has a projection.
In conclusion, the hypothesis of this experiment is to examine during which performance is the BLA is more active: the goal-directed or habitual behavior. In other words, the aim is to see after which train session, there is more overlap of c-Fos and the retrograde tracer, the goal-directed or habitual behavior.
II. Objective
Detect the activated cells during the performance of goal-directed and habitual behaviors by observing the co-expression of c-Fos and retrograde tracer, in which activated neurons and projections are reflected. Specifically focusing on the projections from the basolateral amygdala to the nucleus accumbens to testhow they are differentially engaged during the performance of habitual versus goal-directed behavior.
