BRAIN Initiative K99 Project

BRAIN Initiative K99 项目

• 批准号: 10710507
• 负责人: Veronica A Alvarez
• 金额: $ 4.83万
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10710507
• 关键词: Animals; BRAIN initiative; Behavioral; Brain; Brain region; Complex; Corpus striatum structure; Costs and Benefits; Data; Dopamine; Dopamine D2 Receptor; Eating; Energy Intake; Food; Food Intake Regulation; Hypothalamic structure; Insulin; Lateral; Link; Measurement; Motivation; Mus; Neurons; Nucleus Accumbens; Pathway interactions; Rewards; Role; Self Administration; Signal Transduction; Slice; Techniques; Training; behavioral economic analysis; cell type; energy balance; experimental study; feeding; food consumption; hedonic; neuronal circuitry

In accordance with aims of the proposal, the following experiments were done to determine the role of dopamine D2 receptor (D2R) containing neurons in the nucleus accumbens (NAc) in food intake: 1- Assessing motivation to seek and consume food in animals with low D2R in the striatum. Behavioral experiments using operant food self-administration in mice with targeted deletion of Drd2 and littermate controls. Behavioral economic analysis using progressive ratio responding to increase the effort required to obtain a single food pellet (reward) allows us to calculate the cost-benefit function. Experiments are still underway. Preliminary data shows changes in motivation associated with low levels of D2R in the striatum. 2. Measurements of evoked dopamine signals in brain slices from mice with low D2R and littermate controls. We are evaluating the effect of insulin on the dopamine signals and the changes in the insulin effect when D2R levels are decreased.

根据该提案的目的，进行了以下实验以确定多巴胺D2受体（D2R）在食物摄入中的作用，多巴胺D2受体（D2R）在丘脑核（NAc）中含有神经元： 1-在纹状体中具有低D2R的动物中评估寻找和消耗食物的动机。在具有Drd2靶向缺失的小鼠和同窝对照中使用操作性食物自我给药的行为实验。行为经济学分析使用累进比率响应增加获得单个食物颗粒（奖励）所需的努力，使我们能够计算成本效益函数。实验仍在进行中。初步数据显示，动机的变化与纹状体中低水平的D2R有关。 2.低D2R小鼠和同窝对照小鼠脑切片中诱发多巴胺信号的测量。我们正在评估胰岛素对多巴胺信号的影响以及当D2R水平降低时胰岛素效应的变化。

项目成果

Serotonin receptors contribute to dopamine depression of lateral inhibition in the nucleus accumbens.

• DOI: 10.1016/j.celrep.2022.110795
• 发表时间: 2022-05-10
• 期刊: CELL REPORTS
• 影响因子: 8.8
• 作者: Burke, Dennis A.;Alvarez, Veronica A.
• 通讯作者: Alvarez, Veronica A.

Striatopallidal neurons control avoidance behavior in exploratory tasks.

• DOI: 10.1038/s41380-018-0051-3
• 发表时间: 2020-02
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: LeBlanc KH;London TD;Szczot I;Bocarsly ME;Friend DM;Nguyen KP;Mengesha MM;Rubinstein M;Alvarez VA;Kravitz AV
• 通讯作者: Kravitz AV