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。人类功能磁共振成像和LFP记录研究表明，前脑岛编码了 刺激和偏离预期。然而，大胆的信号和LFP没有足够的分辨率来评估 这些代码是如何在岛状细胞中分布的。此外，岛屿的起源和功能相关性 密码尚不清楚。我们将通过多站点单单元和LFP录音以及 大鼠的光遗传学方法。关键的是，我们的试点数据表明，显著刺激的呈现会引起相同的结果 大鼠和人类的LFP反应：爆发高幅度的β(13-30赫兹)振荡。 意义和方法。因为在大多数精神疾病中，脑岛的体积会缩小，所以脑岛是一种 有望成为经颅或脑深部刺激的治疗靶点。然而，在这一领域取得了进展 由于缺乏关于岛信号的高分辨率数据而受阻。因此，这项提案可能会促进 开发新的治疗方法。为了研究大鼠的脑岛，我们开发了一种新的强化学习任务 它以老鼠的期望(以及它们的违规行为)的行为读数为特色。这项任务将使我们能够评估 前脑岛神经元及其突触伙伴如何编码多个变量，并探索它们在学习中的作用。 目的#1描述前脑岛及其突触伙伴神经元的编码特性。 我们将在前岛叶及其突触伙伴进行多点单位和LFP记录。这将允许 美国将：(1)测试这些不同部位的细胞是否编码结果的价态、大小、显著程度和偏差 从预期中；(2)测试配价刺激是否在前脑岛引起爆发的β振荡，如图所示 (3)比较不同频率的振荡对神经元在这些不同部位的夹带； (4)测试岛状贝塔爆发的幅度是否跟踪刺激的突出性和偏离预期。 目的#2：确定哪些输入驱动前岛叶神经元中不同变量的编码。数据 在目标1中获得的信息将表明哪些输入向岛神经元传达了关于不同变量的信息。类似 关于岛状贝塔爆发的起源和传播的假说将会出现。为了检验这些假设，我们 将注入AAVs，驱动投射定义的细胞类型中抑制视蛋白的表达。那么，我们就会抑制 候选细胞类型并评估这些操作如何影响岛神经元的编码特性 以及岛状贝塔爆发的发生和传播。 目的#3测试减少或增强胰岛β爆发是否会损害或促进学习。我们会 光遗传学与可编程多通道相结合实现对岛状贝塔爆发的实时控制 信号处理器，给了我们前所未有的对快速神经元活动的控制。我们将加强或削弱 通过提供低强度光刺激来产生岛状β爆发，从而使尖峰时间相对于 在不改变射速的情况下，贝塔振荡。如果岛状贝塔病毒爆发促进学习，则上调或下调它们 在任务中应分别加速或减慢学习。