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Corticostriatal circuits in behavioral flexibility

行为灵活性中的皮质纹状体回路

基本信息

批准号：
9403124
负责人：
Kristen Marie Delevich
金额：
$ 0.06万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-12-01 至 2017-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9403124
关键词：
Adolescence Adolescent Adult Animals Anterior Basal Ganglia Behavior Behavioral Behavioral Model Brain Cognitive Community Health Contralateral Corpus striatum structure DRD2 gene Data Decision Making Development Discrimination Disease Dopamine D1 Receptor Dopamine D2 Receptor Dorsal Electrophysiology (science)Environment Equilibrium Exhibits Feedback Functional disorder Genetic Variation Goals Human Genetics Impaired cognition Impairment In Vitro Individual Ipsilateral Learning Link Measures Mediating Mental disorders Methods Movement Mus Neurons Outcome Pathway interactions Pharmacology Phase Process Property Punishment Reversal Learning Rewards Role Schizophrenia Signal Transduction Specificity Synapses Time Training Update Variant Weight addiction avoidance behavior base cell type experimental study flexibility in vivo innovation insight neural circuit public health relevance receptor expression relating to nervous system response success tool transmission process

项目摘要

DESCRIPTION (provided by applicant): Successful goal-directed behavior requires the ability to select actions that result in reward and avoid actions that result in no reward, or worse, punishment. In the real world, the rules that link actions and their outcomes often change, such that an action that was once rewarded ceases to be so and vice versa. The ability to update decision-making strategy based on positive or negative feedback is the basis for behavioral flexibility. A balance in the weighting of positive and negative feedback's influence over choice selection may be vital for optimal decision-making. It is believed that in disease such as addiction, the ability to learn from negative feedback becomes blunted and reward-seeking overrides normal decision-making processes (Cox et al., 2015; Parvaz et al., 2015). It is well-known that addiction is associated with lower D2 receptor expression in the striatum (Bowirrat et al., 2005; Goldstein and Volkow, 2011; Besson et al., 2013). Previous data from our lab and others implicate D2 receptor-expressing medium spiny neurons (MSNs) of the dorsomedial striatum (DMS) in signaling non-rewarded outcomes and promoting avoidance behavior (Kravitz et al., 2012; Tai et al., 2012). However, the causal role of D2 MSNs in learning from positive and negative outcomes remains unknown. Understanding the contribution of D2 MSN activity to behavioral flexibility will illuminate neural circuit mechanisms that underlie impaired flexibility seen in several psychiatric disorders. I propose to study learning-induced plasticity in the corticostriatal microcircuit to determine if there is a neural signature for behavioral flexibility I will record channelrhodopsin evoked excitatory transmission from the dorsal anterior cingulate (dACC) to the DMS onto D1 or D2 MSNs following the discrimination or reversal phase in a lateralized two-choice decision-making task (Aim 1). Furthermore, I will compare corticostriatal transmission in adults to juveniles, who enact more efficient reversal learning. Next, I will employ chemogenetic tools to selectively inhibit or excite D2 MSNs during a T-maze based spatial reversal task, a 4 choice nonspatial reversal task, and a probabilistic switching task, tha all require flexible updating of decision-making strategies, albeit across different cognitive domains and time-scales (Aim 2). These data will contribute to establishing the striatal circuit mechanisms that support flexible decision-making and reversal learning. By comparing juvenile and adult mice, these experiments will also help to establish how corticostriatal circuits mature during adolescence to alter decision-making strategies. My sponsors and I anticipate that our highly controlled, sensitive, and cell-type specific experimental data from mice will help the larger health community understand the neural basis of impairments in behavioral flexibility. In addition, it may also illuminate a neural basis to developmental changes learning from positive versus negative feedback.