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所有加拿大人。百分之二十的加拿大人在一生中会亲身经历精神疾病。精神疾病对个人、家庭和卫生保健系统来说代价高昂。根据多伦多大学公共卫生科学系的估计，加拿大精神健康问题的年度经济影响为144亿美元（Stephens & Joubert，Chronic Dis Can，2001，22：18）。1999年，加拿大普通医院所有入院病人中有3.8%（150万住院日）是由于焦虑症、双相情感障碍、精神分裂症、严重抑郁症、饮食失调和自杀行为。以上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的问题，都意味着在脑核（Acb）水平上的一些不便，这是一个前脑区域，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的并行通路，处理特定的信息的特定子集的Acb神经元的人口，但解剖方面和生理机制，这些功能集群的Acb还不清楚。本项目将研究多巴胺的相互作用和调制的信号来自前额叶皮层和内侧丘脑（可能与动机和压力）的特定人口的Acb神经元，支配外侧下丘脑和潜在的影响进食。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记录，和（B）形态学实验，以获得新的见解的突触连接的Ac B。在这些实验中获得的知识将有助于治疗焦虑症（占加拿大人估计患病率的12.2%）和饮食失调症（厌食症和贪食症;分别影响2.5%的妇女和0.3%的男子;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).