Opposing Roles of Distinct Output Projections From Prefrontal Cortex

前额皮质不同输出投射的相反作用

• 批准号: 8797307
• 负责人: RACHEL J SMITH
• 金额: $ 19.77万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8797307
• 关键词: Anterior; Area; Basic Science; Behavior; Behavioral; Behavioral inhibition; Cell Nucleus; Cocaine; Conceptions; Cues; Data; Decision Making; Drug Addiction; Employee Strikes; Evaluation; Exhibits; FOS gene; Foundations; Freezing; Fright; Functional disorder; Future; Health; Individual; Investigation; Label; Motor Cortex; Mus; Mutate; Neurons; Neurosciences; Nucleus Accumbens; Output; Pattern; Pharmaceutical Preparations; Play; Population; Prefrontal Cortex; Process; Rabies virus; Rattus; Red nucleus structure; Relapse; Research; Rodent Model; Role; Self Administration; Source; Structure; Synapses; Technology; Testing; Thalamic structure; Theoretical model; Tracer; Viral; Work; addiction; base; behavioral response; cognitive process; conditioned fear; design; frontal lobe; improved; nerve supply; novel; optogenetics; research study

DESCRIPTION (provided by applicant): Prefrontal cortex (PFC) dysfunction is thought to underlie many of the maladaptive behaviors that characterize addiction. Although many studies have investigated how subregions of PFC contribute to cognitive processing and drug seeking, very few studies have examined the functional contribution of individual layers. PFC projection neurons are segregated by their output targets, including segregated sublayers within prelimbic PFC projecting to nucleus accumbens (NAc) core vs. rostromedial tegmental nucleus (RMTg), two structures that often have opposing influences on behavior in rats, including those associated with fear and drug seeking. The current set of studies is aimed at testing the novel hypothesis that projection neuron sublayers are an important organizational feature of PFC, and that sublayer differences in afferents, efferents, and function are critical to the diverse functionality of PFC across a range of behavioral responses. The functional role played by projection neuron sublayers in PFC has been overlooked in addiction studies, and further studies of both the behavioral function and anatomical connectivity are necessary for understanding the role that PFC dysfunction plays in addiction. The first aim of the application will investigate whether PFC projection neuron sublayers projecting to NAc vs. RMTg have independent and dissociable contributions to behavior. These studies will use rodent models of relapse and fear: reinstatement of cocaine seeking in a self-administration paradigm (cue-induced lever pressing), and conditioned fear (cue-induced freezing). c-Fos activation patterns in retrogradely-labeled PFC neurons will be used to determine independent function, and optogenetic inhibition of PFC terminals in NAc vs. RMTg will be used to test opposing functional contributions of these two sublayers. The second aim of the application will use trans-synaptic retrograde tracing technology to investigate differences in afferent connectivity to PFC sublayers projecting to either NAc or RMTg. These basic research studies will demonstrate that projection neuron sublayers in PFC have dissociable roles in addiction, and that discrete segmentation of output projection subpopulations is a key component of PFC organization and function that has been overlooked previously.

描述（由申请人提供）：前额皮质（PFC）功能障碍被认为是许多成瘾特征的适应不良行为的基础。尽管许多研究已经调查了 PFC 的子区域如何促进认知处理和药物寻求，但很少有研究检查各个层的功能贡献。 PFC 投射神经元按其输出目标进行隔离，包括投射到伏隔核 (NAc) 核心与喙内侧被盖核 (RMTg) 的前边缘 PFC 内的隔离亚层，这两种结构通常对大鼠的行为产生相反的影响，包括与恐惧相关的行为和寻求毒品。目前的一组研究旨在测试新的假设，即投射神经元子层是 PFC 的一个重要组织特征，并且传入神经、传出神经和功能的子层差异对于 PFC 在一系列行为反应中的多样化功能至关重要。在成瘾研究中，PFC 中投射神经元亚层所发挥的功能作用一直被忽视，为了理解 PFC 功能障碍在成瘾中所起的作用，有必要对行为功能和解剖连接进行进一步研究。该应用程序的第一个目标将调查投射到 NAc 与 RMTg 的 PFC 投射神经元子层是否对行为具有独立且可分离的贡献。这些研究将使用复发和恐惧的啮齿动物模型：在自我管理范式中恢复可卡因寻求（提示诱导的杠杆按压）和条件性恐惧（提示诱导的冻结）。逆行标记的 PFC 神经元中的 c-Fos 激活模式将用于确定独立功能，NAc 与 RMTg 中 PFC 末端的光遗传学抑制将用于测试这两个亚层的相反功能贡献。该应用程序的第二个目标将使用跨突触逆行追踪技术来研究投射到 NAc 或 RMTg 的 PFC 子层的传入连接差异。这些基础研究将证明 PFC 中的投射神经元子层在成瘾中具有可分离的作用，并且输出投射亚群的离散分割是 PFC 组织和功能的关键组成部分，但之前一直被忽视。

项目成果

Prelimbic cortical projections to rostromedial tegmental nucleus play a suppressive role in cue-induced reinstatement of cocaine seeking.

前边缘皮质投射到嘴内侧被盖核，在提示诱导的可卡因寻求恢复中发挥抑制作用。

• 发表时间: 2021
• 作者: Cruz, Adelis M;Spencer, Haley F;Kim, Tabitha H;Jhou, Thomas C;Smith, Rachel J
• 通讯作者: Smith, Rachel J

Monosynaptic Retrograde Tracing From Prelimbic Neuron Subpopulations Projecting to Either Nucleus Accumbens Core or Rostromedial Tegmental Nucleus.

从投射到伏核核心或吻内侧被盖核的前边缘神经元亚群的单突触逆行追踪。

• 发表时间: 2021
• 作者: Cruz, Adelis M;Kim, Tabitha H;Smith, Rachel J
• 通讯作者: Smith, Rachel J

The Role of the Cortex-Dorsal Striatum Pathway in Morphine-Induced Compulsive Drug Seeking and Taking Behaviors

皮质-背侧纹状体通路在吗啡诱导的强迫性药物寻求和服用行为中的作用

• DOI: 10.1037/a0034575
• 发表时间: 2013-12
• 期刊: Experimental and clinical psychopharmacology
• 影响因子: 2.3
• 作者: Anderson, Brian A.;Faulkner, Monica L.;Rilee, Jessica J.;Yantis, Steven;Marvel, Cherie L.
• 通讯作者: Marvel, Cherie L.