Cortical assembly formation through excitatory/inhibitory circuit plasticity

通过兴奋/抑制回路可塑性形成皮质组件

• 批准号: 10729689
• 负责人: Brent D. Doiron
• 金额: $ 207.83万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10729689
• 关键词: Area; Behavior; Brain; Cells; Computational Technique; Computer Models; Data; Discrimination; Disinhibition; Electrodes; Equilibrium; Goals; Interneurons; Joints; Learning; Mediating; Memory; Modeling; Neurodegenerative Disorders; Neurons; Odors; Olfactory Cortex; Olfactory Pathways; Parvalbumins; Performance; Play; Population; Process; Recurrence; Rewards; Role; Sensory; Somatostatin; Stimulus; Structure; Synapses; Synaptic plasticity; Testing; Theoretical Studies; Theoretical model; Training; Vasoactive Intestinal Peptide; hippocampal pyramidal neuron; insight; learned behavior; neural; neuroimaging; neuronal cell body; olfactory stimulus; piriform cortex; programs; response; statistics; theories

Cortical assembly formation through excitatory/inhibitory circuit plasticity. Project Summary Throughout the brain, sensory information is thought to be represented by the joint activity of neurons that form functionally connected assemblies. A long-standing premise is that assemblies are formed during sensory learn- ing by strengthening the excitatory connections between co-active neurons. However, the role of inhibition in this process has yet to be fully elucidated. In this proposal, we will investigate the inhibitory and disinhibitory circuits that underlie the formation, stabilization and competition between neural assemblies. However, the con- tributions of specific interneuron classes to these processes is unknown. We have developed a theoretical model of assembly formation that incorporates data driven inhibitory synaptic plasticity rules for Parvalbumin (PV) and Somatostatin (SOM) expressing interneurons. Two key predictions arise from this model. First, PV interneu- rons provide inhibition that scales with excitation to stabilize neural assemblies. And second, SOM interneurons mediate competition between assemblies. In this proposal, we aim to experimentally test these predictions. In the olfactory cortex, we have found that odor discrimination training promotes assembly formation in response to rewarded odors but not unrewarded odors. In addition, we find that inhibition scales with excitation in the rewarded assembly. Thus, the olfactory cortex provides an ideal substrate to test predictions about the specific roles of PV and SOM neurons in assembly competition and stabilization. In Aim 1, we investigate the role of PV interneurons in maintaining excitation and inhibition balance and stabilizing rewarded assemblies. In Aim 2, we investigate the role for SOM interneurons in mediating inter-assembly competition. Finally, we have shown that a disinhibitory circuit mediated by vasoactive intestinal peptide (VIP) interneurons, gates recur- rent excitatory plasticity onto pyramidal neurons. This suggests an intriguing hypothesis that VIP interneurons inhibit SOM interneurons to promote the specific formation of the rewarded assembly. In Aim 3, we will use a combined theoretical and experimental approach to investigate the role of VIP-cell mediated disinhibition in gating assembly formation. The studies outlined in this proposal take a comprehensive approach to investigating the synaptic and circuit mechanisms that underlie assembly activity in the cortex. We focus on circuit motifs that are found in all cortices and we expect our findings will have broad impact across brain areas. Our findings will illuminate the important roles inhibitory and disinhibitory circuits play in assembly dynamics during sensory-guided behavior.

通过兴奋/抑制回路可塑性的皮质组装形成。 项目摘要 在整个大脑中，感觉信息被认为是由神经元的联合活动来表示的， 功能性连接的组件。一个长期存在的假设是，组装是在感官学习过程中形成的- 通过加强共同活动的神经元之间的兴奋性连接。然而，抑制在 这一过程还有待充分阐明。在这个建议中，我们将研究抑制和去抑制 构成神经组装体之间的形成、稳定和竞争基础的回路。然而，骗局-- 特定的中间神经元类对这些过程的贡献是未知的。我们建立了一个理论模型 组装形成，包括数据驱动的抑制性突触可塑性规则的小清蛋白（PV）和 生长抑素（SOM）表达的中间神经元。两个关键的预测来自这个模型。第一，光伏互联网- RON提供抑制，其与兴奋成比例以稳定神经组装。其次，SOM中间神经元 协调各组件之间的竞争。在这个提议中，我们的目标是通过实验来测试这些预测。在 在嗅觉皮层，我们发现气味辨别训练促进了反应中的组装形成， 而不是不受欢迎的气味。此外，我们发现，抑制规模与兴奋中， 奖励集会因此，嗅觉皮层提供了一个理想的基底来测试对特定的 PV和SOM神经元在组装竞争和稳定中的作用。在目标1中，我们研究了 PV中间神经元在维持兴奋和抑制平衡以及稳定奖赏组装中的作用。在 目的2：研究SOM中间神经元在介导组装竞争中的作用。最后我们 已经表明，由血管活性肠肽（VIP）中间神经元介导的去抑制回路，门复发， 将兴奋性可塑性传递给锥体神经元。这提出了一个有趣的假设，VIP中间神经元 抑制SOM中间神经元，促进奖励组装的特异性形成。在目标3中，我们将使用 结合理论和实验方法来研究VIP细胞介导的去抑制作用 在浇口组件形成中。 在这项建议中概述的研究采取了全面的方法来调查突触和电路 大脑皮层组装活动的基础机制。我们专注于在所有皮层中发现的电路图案 我们希望我们的发现将对大脑各区域产生广泛的影响。我们的发现将阐明 在感觉引导的行为过程中，抑制和去抑制回路在组装动力学中的作用。