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.

项目概要 侧隔膜（LS）是一个神秘的大脑区域，它有助于多种行为和 与包括焦虑在内的许多精神疾病有关。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，这些研究的结果常常是相互矛盾的。 LS 的早期研究 将其分为不同的解剖学子区域，表明其子区域在调解中的假定作用 不同的功能。最近的研究重新审视了这项早期的工作，并假设有 LS 内的功能亚基，可能会选择不同的行为结果。这 该提案旨在通过表征解剖组织、神经编码来解决这一理论 两个 LS 投影总体的属性和函数。我将特别关注两个目标区域 接收来自侧隔膜的输入并体现了 LS 的功能多样性：腹侧 被盖区 (VTA) 因其在奖励表征和纹状体床核中的作用而闻名 Terminalis (BNST) 因其在提示编码中的作用而闻名。在目标 1 中，我将执行特定于细胞的投影 在一系列操作行为范式中进行分辨率钙成像，以评估每个行为范式的作用 奖励相关行为的预测人群。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 将编码奖励相关信息，LS-BNST 将编码奖励线索。在目标 2 中，我 将使用特定于投影的闭环光遗传学操作来确定 LS-VTA 和 LS-BNST 在不同训练的奖励相关行为中的投影群体。我会 量化这两个群体的抑制对操作者不同行为结果的影响 分析，这将深入了解这些 LS 亚群在功能上的差异。结果 该提案将提供关于 LS 如何运作的更完整视图，特别是在奖励方面 相关行为。它将进一步我们对一个无法解释的大脑区域的理解 多年来，它可能被证明是治疗各种精神疾病的重要目标。