SIGNALING OF SALIENCE AND PREDICTION ERRORS BY THE INSULA

脑岛发出的显着信号和预测误差

• 批准号: 10656971
• 负责人: DENIS PARE
• 金额: $ 39.25万
• 依托单位: RUTGERS THE STATE UNIV OF NJ NEWARK
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10656971
• 关键词: Acceleration; Address; Affect; Anterior; Area; Automobile Driving; Behavioral; Cells; Cephalic; Code; Cognitive; Computers; Data; Deep Brain Stimulation; Development; Emotions; Event; Frequencies; Functional Magnetic Resonance Imaging; Human; Impairment; Insula of Reil; Interoception; Learning; Light; Mediating; Mental disorders; Methods; Neurons; Opsin; Outcome; Phase; Physiological; Process; Property; Psychological reinforcement; Rattus; Resolution; Resources; Rewards; Role; Signal Transduction; Site; Stimulus; Synapses; Techniques; Testing; Therapeutic Intervention; Time; cell type; expectation; experimental study; insight; light intensity; novel; novel therapeutics; optogenetics; recruit; response; targeted treatment; therapeutic target

Overview. Human fMRI and LFP recording studies suggest that the anterior insula encodes the salience of stimuli and deviations from expectations. However, BOLD signals and LFPs have insufficient resolution to assess how these codes are distributed across insular cells. Moreover, the origin and functional relevance of insular codes is unclear. We will address these questions with multi-site single unit and LFP recordings as well as optogenetic methods in rats. Critically, our pilot data indicates that presentation of salient stimuli elicits identical LFP responses in rats and humans: bursts of high amplitude beta (13-30 Hz) oscillations. Significance and approach. Because its volume is reduced in most psychiatric disorders, the insula is a promising therapeutic target for transcranial or deep brain stimulation. However, progress in this field has been hindered by a lack of high-resolution data about insula signaling. Thus, this proposal may facilitate the development of novel therapies. To study the insula in rats, we developed a novel reinforcement learning task that features a behavioral readout of the rats’ expectations (and their violations). This task will allow us to assess how anterior insula neurons and their synaptic partners encode multiple variables and probe their role in learning. Aim #1 Characterize the coding properties of neurons in the anterior insula and its synaptic partners. We will perform multi-site unit and LFP recordings in the anterior insula and its synaptic partners. This will allow us to: (1) test whether cells at these various sites encode outcome valence, magnitude, salience, and deviations from expectations; (2) test whether valenced stimuli elicit bursts of beta oscillations in the anterior insula, as seen in humans; (3) compare the entrainment of neurons at these various sites by oscillations of different frequencies; (4) test whether the amplitude of insular beta bursts tracks stimulus salience and deviations from expectations. Aim #2: Determine which inputs drive coding of different variables in anterior insula neurons. The data obtained in Aim 1 will suggest which inputs convey information about different variables to insula neurons. Similar hypotheses will arise regarding the origin and propagation of insular beta bursts. To test these hypotheses, we will infuse AAVs driving the expression of an inhibitory opsin in projection-defined cell types. Then, we will inhibit the candidate cell types and assess how these manipulations affect the coding properties of insula neurons as well as the genesis and propagation of insular beta bursts. Aim #3 Test whether reducing or enhancing insular beta bursts impairs or facilitates learning. We will achieve real-time control over insular beta bursts by combining optogenetics with programmable multi-channel signal processors, giving us unprecedented control over fast neuronal events. We will enhance or dampen insular beta bursts by delivering low-intensity light stimuli that bias spike times in or out-of-phase with respect to beta oscillations, without altering firing rates. If insular beta bursts facilitate learning, up- or down-regulating them should respectively accelerate or slow down learning in the task.

概述。人类fMRI和LFP记录研究表明，前岛岛的显着性 刺激和偏离期望。但是，大胆的信号和LFP的评估分辨率不足 这些代码如何分布在岛状细胞之间。此外，岛屿的起源和功能相关性 代码不清楚。我们将使用多站点的单个单元和LFP录音以及 大鼠的光遗传学方法。至关重要的是，我们的飞行员数据表明​​，显着刺激的表现相同 大鼠和人类的LFP反应：高振幅β（13-30 Hz）振荡的爆发。 意义和方法。因为大多数精神疾病的体积减少了，所以岛是一个 有希望的经颅或深脑刺激的治疗靶标。但是，该领域的进展一直在 由于缺乏有关岛信号传导的高分辨率数据而阻碍。那，该提议可能有助于 新疗法的发展。为了研究老鼠的绝缘体，我们开发了一项新颖的增强学习任务 这是对大鼠期望（及其违规行为）的行为读数。这项任务将使我们能够评估 前岛神经元及其突触伙伴如何编码多个变量并探究其在学习中的作用。 AIM＃1表征神经元及其突触伙伴中神经元的编码属性。 我们将在前岛及其突触伙伴中执行多站点单元和LFP记录。这将允许 我们要：（1）测试这些各个地点的单元格是否编码结果价，大小，显着性和出发 从期望（2）测试评估刺激是否会引起前岛的β振荡爆发，如所见 在人类中； （3）通过不同频率的振荡比较这些位点的神经元的入口； （4）测试Insular beta爆发的放大器是否跟踪刺激显着性并偏离预期。 AIM＃2：确定前岛神经元中不同变量的哪些输入驱动编码。数据 在AIM 1中获得的将表明哪些输入传达了有关岛神经元不同变量的信息。相似的 关于岛屿beta爆发的起源和传播，将出现假设。为了检验这些假设，我们 将在投影定义的细胞类型中注入AAVS驱动抑制性蛋白的表达。然后，我们将抑制 候选细胞类型和评估这些操作如何影响岛神经元的编码特性 以及岛屿beta爆发的起源和传播。 目标＃3测试减少或增强岛屿β爆发会损害还是促进学习。我们将 通过将光遗传学与可编程多通道相结合，实现对岛屿β爆发的实时控制 信号处理器，使我们对快速神经元事件的空前控制。我们将增强或抑制 通过传递低强度的光刺激来使岛屿beta爆发，从而使相对于相位或相位的差异降低。 β振荡，没有改变点火率。如果岛上的beta爆发了最喜欢的学习，将其上调或下调 应该分别加速或减慢任务学习。