Examining the neural substrates of reward in the lateral septum

检查外侧隔膜中奖赏的神经基质

• 批准号: 10751657
• 负责人: Jennifer Samantha Isaac
• 金额: $ 4.77万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-11 至 2026-08-10
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751657
• 关键词: Address; Anatomy; Anxiety; Behavior; Behavioral; Behavioral Paradigm; Biological Assay; Brain region; Calcium; Cues; Disease; Dissection; Electric Stimulation; Event; Feeding behaviors; Future; Genetic; Head; Heterogeneity; Hippocampus; Hypothalamic structure; Image; Label; Lateral; Lesion; Literature; Mediating; Mental disorders; Methods; Microscope; Motivation; Mus; Neurons; Pathway interactions; Phenotype; Population; Population Projection; Positioning Attribute; Property; Research; Research Personnel; Resolution; Rewards; Role; Self Stimulation; Series; Structure of terminal stria nuclei of preoptic region; Target Populations; Training; Ventral Tegmental Area; Viral; Visit; With laterality; Work; behavioral outcome; disorder prevention; hedonic; imaging study; insight; motivated behavior; neural; neural circuit; neural correlate; new therapeutic target; novel; novel therapeutic intervention; optogenetics; prevent; reinforced behavior; reward processing; sensor; theories; tool

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.

项目摘要 外侧隔（LS）是一个神秘的大脑区域，有助于多种行为， 与包括焦虑在内的多种精神疾病有关几十年来， 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是相互矛盾的。LS的早期研究 将其分为不同的解剖亚区，表明其亚区在介导 不同的功能。最近的研究重新审视了这一早期的工作，并假设有 LS内的功能亚单位，其可以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 性质和两个LS投影总体的函数。我将特别侧重于两个目标区域 接受来自外侧隔的输入，并支持LS的功能多样性：腹侧 被盖区（VTA），以其在奖赏表征中的作用和纹状体的床核而闻名 终末细胞（BNST），以其在线索编码中的作用而闻名。在目标1中，我将执行投影特定的细胞 在一系列操作性行为范例中进行分辨率钙成像，以评估每种 奖励相关行为的预测人群。我假设每个预测人口将 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将对奖励相关信息进行编码，LS-BNST将对奖励提示进行编码。在目标2中，我 将使用投射特异性，闭环光遗传学操作来确定 LS-VTA和LS-BNST投射群体在不同训练的奖励相关行为中的作用我会 量化这两个群体的抑制对不同行为结果的影响 分析，这将提供洞察这些LS亚群是如何在功能上不同。结果 从这个建议将提供一个更完整的视图如何LS功能，特别是在奖励- 相关行为。这将进一步加深我们对大脑区域的理解， 多年来，它可能被证明是治疗各种精神疾病的关键目标。