Cortical assembly formation through excitatory/inhibitory circuit plasticity

通过兴奋/抑制回路的可塑性形成皮质组装。 项目摘要 在整个大脑中，感觉信息被认为是由形成的神经元的联合活动来表示的 功能连接的程序集。一个由来已久的前提是，组装是在感官学习过程中形成的-- ING通过加强共同活动神经元之间的兴奋性连接。然而，抑制在生物多样性中的作用 这一过程尚未完全阐明。在本提案中，我们将研究抑制和非抑制 构成神经集合体之间形成、稳定和竞争的回路。然而，这个骗局- 特殊的fic中间神经元类对这些过程的贡献尚不清楚。我们开发了一个理论模型 结合了数据驱动的针对小白蛋白(PV)的抑制性突触可塑性规则和 生长抑素(SOM)表达中间神经元。从这个模型中可以得出两个关键预测。第一，光伏中间- RON提供随着兴奋而调节的抑制，以稳定神经集合体。第二，SOM中间神经元 调解程序集之间的竞争。在这项提案中，我们的目标是对这些预测进行实验测试。在……里面 嗅觉皮层，我们发现气味辨别训练促进了组装的形成 有奖赏的气味，但不是没有奖赏的气味。此外，我们还发现，在fi中，抑制程度随激发程度而变化 有奖励的集会。因此，嗅觉皮质提供了一个理想的底物来测试对特定fic的预测。 PV和SOM神经元在组装竞争和稳定中的作用。在目标1中，我们调查了 PV中间神经元在维持兴奋和抑制平衡以及稳定奖赏集合体中的作用。在……里面 目的2，我们研究了SOM中间神经元在调节装配间竞争中的作用。最后，我们 已有研究表明，血管活性肠肽(VIP)中间神经元介导的去抑制环路、GATES重现。 将兴奋性可塑性租给锥体神经元。这表明了一个耐人寻味的假设，即VIP中间神经元 抑制细胞外膜中间神经元促进奖赏集合体的特异性fic的形成。在目标3中，我们将使用 用理论和实验相结合的方法研究VIP细胞介导的去抑制作用 在浇注组件形成过程中。 这项提案中概述的研究采用了一种综合的方法来研究突触和环路 大脑皮层组装活动的基础机制。我们专注于在所有大脑皮层中发现的电路主题 我们预计，我们的fi结果将对大脑各区域产生广泛影响。我们的fi代码将阐明重要的 在感官引导的行为中，抑制和去抑制回路在装配动力学中发挥作用。

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.