Examining the neural substrates of reward in the lateral septum

项目总结 外侧隔(LS)是一个神秘的大脑区域，它参与了一系列行为和 与包括焦虑症在内的许多精神障碍有关。几十年来， 研究人员试图确定这一大脑区域是如何产生这种功能的 多样性。然而，这些研究的结果往往相互矛盾。最小二乘法的早期研究 将其划分为不同的解剖亚区，表明其亚区在调节 不同的功能。最近的研究重新审视了这一早期的工作，并假设存在 LS内的功能亚基，可能选择不同的行为结果。这 一项提案试图通过描述解剖学组织，神经编码来解决这一理论 两个最小二乘投影群体的性质和函数。我将特别关注两个目标区域 从外侧隔接受输入，并举例说明LS的功能多样性：腹侧 被盖区(VTA)，以其在奖赏表征和纹状体床核中的作用而闻名 终末蛋白(BNST)，因其在线索编码中的作用而闻名。在目标1中，我将执行特定于投影的细胞 分辨率钙成像在一系列可操作的行为范例中评估每一个的作用 与奖励相关的行为中的预测人群。我假设每个预测人口都会 编码不同的任务特征，有助于LS的功能多样性。因此，我预测 LS-VTA将对与奖励相关的信息进行编码，LS-BNST将对奖励线索进行编码。在目标2中，我 将使用特定于投影的闭环光遗传操作来确定 LS-VTA和LS-BNST在不同训练的奖赏相关行为中的投影种群。这就做 量化这两个群体的抑制对操作者不同行为结果的影响 这将为这些LS亚群的功能差异提供深入的了解。结果是 将更全面地了解LS的运作方式，特别是在奖励方面- 相关行为。它将进一步加深我们对大脑区域的理解，该区域一直在逃避对 多年来，它可能被证明是治疗各种精神疾病的关键目标。

PROJECT SUMMARY The lateral septum (LS) is an enigmatic brain region that contributes to a multitude of behaviors and has been implicated in a number of psychiatric disorders including anxiety. Over many decades, researchers have attempted to ascertain how this one brain region gives rise to such functional diversity. However, the results of these studies have often been contradictory. Early studies of the LS divided it into distinct anatomical subregions, suggesting a putative role for its subregions in mediating different functions. Recent research has revisited this earlier work and postulates that there are functional subunits within the LS, which may be selecting for different behavioral outcomes. This proposal seeks to address this theory by characterizing the anatomical organization, neural encoding properties, and function of two LS projection populations. In particular, I will focus on two target regions that receive input from the lateral septum and exemplify the functional diversity of the LS: the ventral tegmental area (VTA) known for its role in reward representation and the bed nucleus of the stria terminalis (BNST) known for its role in cue encoding. In Aim 1, I will perform projection-specific cellular resolution calcium imaging during a series of operant behavioral paradigms to evaluate the role of each projection population in reward-related behavior. I hypothesize that each projection population will encode distinct task features, contributing to the functional diversity of the LS. Thus, I predict that the LS-VTA will encode reward-related information and the LS-BNST will encode reward cues. In Aim 2, I will use projection-specific, closed-loop optogenetic manipulations to determine the causal role of the LS-VTA and LS-BNST projection populations in different trained reward-related behaviors. I will quantify the effects of inhibition of these two populations on different behavioral outcomes on an operant assay, which will provide insight into how these LS subpopulations are functionally distinct. The results from this proposal will provide a more complete view of how the LS functions, specifically in reward- related behaviors. It will further our understanding of a brain region that has evaded explanation for many years and may prove to be a crucial target for the treatment of various psychiatric disorders.