Role of the nucleus accumbens in regulating aggression reward.

 描述（由申请人提供）：患有精神疾病的个体出现异常社会行为的风险增加。不幸的是，虽然存在许多治疗策略来治疗这些疾病，但成功率出奇地低， 精神病诊断。也许不那么令人惊讶的是，抑郁症和自闭症等社交障碍通常具有共同的情感障碍，包括错误归因或适应不良的攻击行为，但目前还不清楚这种共同行为特征背后的神经回路。现在，几个不同的研究表明，适应不良的攻击性可能是由大脑奖励回路的失调引起的。此外，即使在非病理性的形式下，我也承认侵略本身可以加强。尽管有这些证据，我们目前对攻击性行为的奖励成分的神经生物学基础的理解是有限的。这个提议的主要目的是研究大脑奖赏回路如何调节攻击性奖赏。 这项研究将集中在脑桥核，大脑奖励回路的关键节点，以前曾涉及调节社会奖励和厌恶。为了直接解决攻击和奖励之间的联系，我们将使用一个新的行为模型，该模型是基于攻击条件位置偏好（CPP）。在这个模型中，攻击性重复的男性间的社会互动与从属入侵者在一个独特的背景下，导致th的发展攻击CPP的攻击配对的背景。通过一个多学科的研究计划，利用分子技术，唤醒行为的深脑钙成像，和化学遗传学操作，我们将探讨神经核直接通路（多巴胺受体1型表达中型多刺神经元）和间接通路（多巴胺受体1型表达中型多刺神经元）的作用在调节侵略奖励预测。我们假设，这些分子定义的NAc内的亚群差异招募编码侵略奖励，和间接途径可能优先从事表现出CPP行为的侵略性小鼠。初步的数据表明，在侵略性，但不是非侵略性的，小鼠入侵演示激活的丘脑核;此外，侵略CPP的表达是由一个Drd 2 anatognist在侵略性小鼠调制。这一系列的研究试图从机制上确定这些不同的神经元群体是如何被差异地招募来编码攻击性奖励的，以及这些神经元是如何介导对攻击性奖励体验的长期影响的。

 DESCRIPTION (provided by applicant): There is an increased risk for abnormal social behavior in individuals suffering from psychiatric disorders. Unfortunately, while many therapeutic strategies exist to treat such disorders, success rates are surprisingly low regardless of the psychiatric diagnosis. Perhaps less surprising, social disorders such as depression and autism often share common affective symptomatology, including misattributed or maladaptive aggressive behavior, yet it is unclear what neural circuits underlie this shared behavioral feature. Several disparate lines of research now suggest that maladaptive aggression may be caused by dysregulation of brain reward circuitry. Further, even in its non-pathological form, it i accepted that aggression itself can be reinforcing. Despite this evidence, our current understanding of the neurobiological basis of the rewarding component of aggressive behavior is limited. The broad objective of this proposal is to investigate how brain reward circuitry modulates aggression reward. This research will focus on the nucleus accumbens, a key node in brain reward circuitry, which has previously been implicated in regulating social reward and aversion. In order to directly address the connection between aggression and reward we will use a novel behavioral model that is based on aggression conditioned place preference (CPP). In this model, aggressive repeated inter-male social interactions with subordinate intruders in a distinct context lead to th development of aggression CPP to the aggression-paired context. Through a multidisciplinary research plan that utilizes molecular techniques, awake-behaving deep-brain calcium imaging, and chemogenetic manipulations, we will explore the role of the nucleus accumbens direct pathway (dopamine receptor type 1 expressing medium spiny neurons) and indirect pathway (dopamine receptor type 1 expressing medium spiny neurons) projections in regulating aggression reward. We hypothesize that these molecularly defined subpopulations within the NAc are differentially recruited for encoding aggression reward, and that the indirect pathway may be preferentially engaged within aggressive mice exhibiting CPP behavior. Preliminary data demonstrate that the nucleus accumbens is activated by intruder presentations in aggressive, but not non-aggressive, mice; further, expression of aggression CPP is modulated in aggressive mice by a Drd2- anatognist. This series of studies seeks to mechanistically identify how these distinct neuronal populations are differentially recruited for encoding aggression reward, and how these neurons mediate the long-lasting effects on aggression reward experience.