Dopamine gating in the nucleus accumbens: impact to the goal-oriented behavior

伏隔核中的多巴胺门控：对目标导向行为的影响

• 批准号: 327597-2006
• 负责人: Timofeeva, Elena
• 金额: $ 1.29万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=363186
• 关键词: Dopamine; gating; nucleus; accumbens; impact

Mental illnesses indirectly affect all Canadians through illness in a family member, friend or colleague. Twenty percent of Canadians will personally experience a mental illness during their lifetime. Mental illnesses are costly to the individual, the family and the health care system. According to estimation of the Department of Public Health Sciences of the University of Toronto, the annual economic impact of mental health problems in Canada is $14.4 billion (Stephens & Joubert, Chronic Dis Can, 2001, 22: 18). In 1999, 3.8% of all admission in general Canadian hospitals (1.5 million hospital days) were due to anxiety disorders, bipolar disorders, schizophrenia, major depression, eating disorders and suicidal behavior. Listed above severe mental disorders, as well as the troubles in associative learning or attention-deficit hyperactivity disorder all imply some inconveniences at the level of the nucleus accumbens (Acb), a forebrain region relaying the brain structures responsible for motivation and goal-oriented behavior. There is compelling evidence for the parallel pathways through the Acb that process the specific information by particular subset of the population of Acb neurons, but the anatomical aspects and physiological mechanisms of these functional clusters in the Acb are as yet unclear. The present project will study the interaction and modulation by dopamine the signals coming from the prefrontal cortex and medial thalamus (presumably related to motivation and stress) to the specific population of Acb neurons that innervate the lateral hypothalamus and potentially affect feeding. To achieve this goal we will perform (a) electrophysiological experiments in vivo, involving extracellular and intracellular recordings, and (b) morphological experiments to get new insights on the synaptic connectivity of the Acb. Knowledge obtained in these experiments will be helpful for the cases of anxiety disorders (12.2% of estimated prevalence among Canadians) and eating disorders (anorexia and bulimia; affecting respectively 2.5% of women and 0.3% of men; Statistics Canada's Canadian Community Health Survey).

精神疾病通过家庭成员、朋友或同事的疾病间接影响所有加拿大人。20%的加拿大人会在有生之年亲身经历精神疾病。精神疾病对个人、家庭和医疗保健系统来说都是昂贵的。据多伦多大学公共卫生科学系估计，加拿大每年因精神健康问题造成的经济影响为144亿美元(Stephens&Joubert，Chronic Dis Can，2001，22：18)。1999年，加拿大普通医院入院人数的3.8%(150万住院日)是由焦虑症、躁郁症、精神分裂症、严重抑郁症、饮食失调和自杀行为引起的。上面列出的严重精神障碍，以及联想学习或注意力缺陷多动障碍方面的问题，都暗示着伏隔核(ACB)水平的一些不便，ACB是负责传递负责动机和目标导向行为的大脑结构的前脑区域。有令人信服的证据表明，通过ACB的平行通路通过ACB神经元群体的特定子集来处理特定的信息，但ACB中这些功能簇的解剖学方面和生理机制尚不清楚。本项目将研究多巴胺的相互作用和调制，多巴胺的信号来自前额叶皮质和内侧丘脑(可能与动机和压力有关)到支配外侧下丘脑并可能影响摄食的特定ACB神经元群。为了实现这一目标，我们将进行(A)活体电生理实验，包括细胞外和细胞内记录，以及(B)形态学实验，以获得对ACB突触连接的新见解。在这些实验中获得的知识将有助于焦虑症(占加拿大人估计患病率的12.2%)和饮食失调(厌食症和暴食症；分别影响2.5%的女性和0.3%的男性；加拿大统计局的加拿大社区健康调查)。