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

精神疾病通过家庭成员、朋友或同事的疾病间接影响到所有加拿大人。20%的加拿大人在他们的一生中会经历一次精神疾病。精神疾病对个人、家庭和卫生保健系统都是昂贵的。根据多伦多大学公共卫生科学系的估计，加拿大每年心理健康问题的经济影响为144亿美元（Stephens & Joubert，慢性病，2001,22:18）。1999年，加拿大综合医院所有住院病人（150万住院日）中有3.8%是由于焦虑症、躁郁症、精神分裂症、重度抑郁症、饮食失调和自杀行为。上面列出的严重精神障碍，以及联想学习障碍或注意缺陷多动障碍，都意味着伏隔核（Acb）水平上的一些不便，这是一个前脑区域，传递负责动机和目标导向行为的大脑结构。有令人信服的证据表明，通过Acb的平行通路处理Acb神经元群体的特定子集的特定信息，但这些功能簇在Acb中的解剖方面和生理机制尚不清楚。本项目将研究多巴胺对来自前额叶皮层和丘脑内侧（可能与动机和压力有关）的信号与支配外侧下丘脑并可能影响进食的特定Acb神经元群的相互作用和调节。为了实现这一目标，我们将进行(a)体内电生理实验，包括细胞外和细胞内的记录，以及(b)形态学实验，以获得对Acb突触连通性的新见解。在这些实验中获得的知识将有助于治疗焦虑症（占加拿大人中估计患病率的12.2%）和饮食失调症（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）。

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).