Feedforward-feedback integration in the posterior parietal cortex

后顶叶皮层的前馈-反馈整合

基本信息

批准号：
10654017
负责人：
Gyorgy Lur
金额：
$ 39.25万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10654017
关键词：
Action Potentials Afferent Pathways Attention Basic Science Behavior Behavioral Brain Cell physiology Cells Cognitive Color Complex Computer Models Computing Methodologies Data Decision Making Dependence Distant Electrophysiology (science)Exhibits Feedback Foundations Future Genetic Goals Human Impairment Individual Knowledge Measures Memory N-Methylaspartate Neocortex Neurons Outcome Output Parietal Lobe Pathway interactions Pharmacology Play Population Primates Research Rodent Role Sensory Short-Term Memory Signal Transduction Slice Source Specificity Stream Sum Synapses Testing Translational Research Work cell type cognitive process designer receptors exclusively activated by designer drugs expectation experimental study hippocampal pyramidal neuron in vivo information processing insight multimodality multisensory neocortical nerve supply neural neuronal circuitry neuropsychiatric disorder novel optogenetics predictive modeling response sensory feedback sensory input sensory integration superior colliculus Corpora quadrigemina

项目摘要

PROJECT SUMMARY / ABSTRACT Complex behaviors rely on the combination of sensory clues and internal factors like goals, expectations, memories, and attention. A breakdown of these interactions is thought to be at the core of many neuropsychiatric disorders. Sensory information is carried by feedforward inputs while internal factors are conveyed via feedback afferents. Robust evidence from humans, primates, and rodents indicates that sensory and feedback neuronal pathways converge in the posterior parietal cortex (PPC). Indeed, the PPC is thought to be fundamental to an array of cognitive processes including working memory and decision-making. These data suggest that PPC neurons play a key role in integrating sensory and cognitive information streams. Yet, we have a critical gap in our knowledge regarding the synaptic mechanisms integrating feedforward inputs with feedback signals in the PPC. This lack of insight limits our ability to understand how neuronal circuit interactions drive behavior and how impaired integration leads to neuropsychiatric disorders. In preliminary experiments, we used two-color optogenetics to independently control cortical afferent pathways. We discovered that PPC neurons receive direct, monosynaptic innervation from both feedforward and feedback sources. Furthermore, we found marked differences in how functionally distinct subclasses of layer 5 pyramidal neurons integrate inputs from discrete long-range afferents. Specifically, intratelencephalically projecting (IT) cells exhibited nonlinear response enhancement while subcortically projecting extratelencephalic (ET) neurons summed inputs linearly. These data motivate our central hypothesis that cell- type specific integration of feedforward and feedback synapses drives input / output transformations in the PPC. To test this hypothesis, we propose a complementary use of opto- and chemogenetic circuit manipulation, brain slice electrophysiology and computational modelling. First, we will determine the temporal rules governing the interaction of feedback and feedforward afferents in distinct layer 5 projection neurons (Aim 1). Then we will combine two-color optogenetics with circuit specific chemogenetic silencing (DREADDs) to determine how cell-type specific synaptic integration drives the functional output of the PPC network (Aim 2). Finally, we will take advantage of computational methods to determine what ionic conductances underlie the cell-type specificity of feedforward-feedback integration (Aim 3). Completion of this research will provide novel insights into the cellular mechanisms underpinning the interaction of sensory and feedback information streams. This knowledge will further our understanding of the principles that guide information processing in the neocortex and provide the foundation for future basic and translational research.

项目概要/摘要复杂的行为依赖于感官线索和内部因素（如目标、期望、记忆、关注。这些相互作用的崩溃被认为是许多问题的核心神经精神疾病。感觉信息由前馈输入携带，而内部因素则由前馈输入携带。通过反馈传入传递。来自人类、灵长类动物和啮齿类动物的有力证据表明，感官反馈神经元通路汇聚于后顶叶皮层（PPC）。事实上，PPC 被认为是包括工作记忆和决策在内的一系列认知过程的基础。这些数据表明 PPC 神经元在整合感觉和认知信息流中发挥着关键作用。然而，我们在整合前馈的突触机制方面的知识存在严重差距 PPC 中带有反馈信号的输入。这种缺乏洞察力限制了我们理解神经元如何电路相互作用驱动行为以及整合受损如何导致神经精神疾病。在初步实验中，我们使用双色光遗传学来独立控制皮质传入通路。我们发现 PPC 神经元接受来自前馈和单突触的直接神经支配。反馈来源。此外，我们发现第 5 层的功能不同子类之间存在显着差异锥体神经元整合来自离散远程传入的输入。具体来说，端脑内投射（IT）细胞在皮层下投射时表现出非线性响应增强端脑外 (ET) 神经元对输入进行线性求和。这些数据激发了我们的中心假设：细胞前馈和反馈突触的特定类型集成驱动输入/输出转换在竞价排名中。为了检验这一假设，我们提出了光生电路和化学电路的互补使用操作、脑切片电生理学和计算建模。首先，我们将确定时间控制不同第 5 层投射神经元中反馈和前馈传入相互作用的规则（目标 1).然后我们将双色光遗传学与电路特异性化学遗传学沉默（DREADD）相结合确定细胞类型特异性突触整合如何驱动 PPC 网络的功能输出（目标 2）。最后，我们将利用计算方法来确定离子电导的基础前馈-反馈整合的细胞类型特异性（目标 3）。这项研究的完成将提供新颖的深入了解支撑感觉和反馈信息相互作用的细胞机制溪流。这些知识将进一步我们对指导信息处理的原则的理解新皮质，并为未来的基础和转化研究提供基础。