Synaptic mechanisms underlying odor representations in olfactory cortex in vivo

体内嗅皮层气味表征的突触机制

• 批准号: 7647914
• 负责人: Cindy Poo
• 金额: $ 2.97万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-20 至 2010-08-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7647914
• 关键词: Action Potentials; Address; Auditory; Birth; Brain; Cells; Cues; Data; Electrophysiology (science); Event; Flavoring; Histology; Human; Interneurons; Investigation; Lead; Mammals; Membrane; Memory; Morphology; Neonatal; Neurons; Odors; Olfactory Cortex; Output; Pathway interactions; Pattern; Perception; Pharmacology; Play; Process; Property; Public Health; Quality of life; Recruitment Activity; Recurrence; Relative (related person); Role; Rupture; Sensory; Shapes; Structure; Suckling Animals; Synapses; Techniques; Visual Cortex; Whole-Cell Recordings; biocytin; imprint; in vivo; insight; olfactory bulb; olfactory stimulus; reconstruction; response; sensory cortex; sensory stimulus; sensory system; somatosensory; synaptic inhibition; voltage clamp

DESCRIPTION (provided by applicant): The long-term objective of our lab is to understand how olfactory information is processed in the mammalian brain. Understanding synaptic mechanisms that lead to representation of sensory stimuli in primary sensory cortices is important in revealing how the brain encodes our perception of the world. This has been under investigation in the auditory, somatosensory, and visual cortices. However, surprisingly little is known about the basic properties of synaptic inputs and circuits that shape odor-evoked neuronal activity in the olfactory cortex. To address this question, this application focuses on the relative responsiveness ("tuning") of odor-evoked excitatory and inhibitory synaptic currents as well as the olfactory cortical circuitry underlying these relationships. I will use a combination of electrophysiology, pharmacology, and histology techniques. Specifically, I will determine the spiking activity of an olfactory cortical neuron to a panel of odors in cell-attached mode in vivo. Following that, by rupturing the membrane under my cell- attached patch to obtain whole-cell configuration, I will record and characterize excitatory and inhibitory synaptic currents of this neuron to the same panel of odors. I will use pharmacology to determine whether the odor-evoked excitatory activity is contributed by direct sensory afferents or recurrent local intracortical circuitry. In addition, these cells will be filled with biocytin and their morphology reconstructed post hoc, to determine differences in odor-evoked activity for principal cells vs. interneurons, which are the local contributors of odor-evoked excitation and inhibition, respectively. There are three specific aims: AIM1: Determine the excitatory and inhibitory synaptic inputs shaping odor-evoked spike output. AIM2: Characterize the contribution of direct sensory vs. associational synaptic inputs in shaping odor-evoked activity. AIMS: Characterize the differences between odor-evoked responses of principal vs. interneurons. PUBLIC HEALTH RELAVENCE: Odors are strong cues in evoking memories of past events, and play an important role in our perception of flavor, contributing significantly to our quality of life. Intriguingly, neonatal mammals (including humans), use olfactory information to form strong maternal attachments. This olfactory "imprinting" to maternal odors is critical to the initiation of suckling and the animal's survival. It appears that cortical processing of odor information, in contrast to other sensory systems, is both functional and necessary at birth. However, the functional properties of cortical circuits in this powerful and vital sensory system are not well understood. By elucidating the synaptic mechanisms for odor representation, I hope to gain insight into fundamental principals governing cortical processing of olfactory information.

描述（由申请人提供）：我们实验室的长期目标是了解如何在哺乳动物大脑中处理嗅觉信息。了解导致在原发感觉皮层中表示感觉刺激的突触机制对于揭示大脑如何编码我们对世界的看法很重要。这已经在听觉，体感和视觉皮层中进行了研究。然而，令人惊讶的是，关于嗅觉皮层中塑造异味的神经元活性的突触输入和电路的基本特性知之甚少。为了解决这个问题，该应用集中于气味引起的兴奋性和抑制性突触电流的相对反应性（“调整”），以及这些关系下的嗅觉皮质电路。我将结合电生理学，药理学和组织学技术。具体而言，我将在体内确定嗅觉皮质神经元对异味的面板的尖峰活性。之后，通过在我的细胞附着的斑块下破裂膜以获得全细胞构型，我将记录并将该神经元的兴奋性和抑制性突触电流表征到同一气味面板。我将使用药理学来确定气味诱发的兴奋活动是由直接感觉传入或复发性局部局部内回路贡献的。此外，这些细胞将充满生物细胞及其形态在事后重建，以确定主细胞与中间神经元的气味诱发活性的差异，这些神经元分别是气味引起的激发和抑制的局部贡献者。有三个特定的目的：AIM1：确定刺激和抑制性突触输入，以塑造气味诱发的尖峰输出。 AIM2：表征直接感觉与关联突触输入在塑造气味诱发活性中的贡献。目的：表征原理与中间神经元的气味诱发响应之间的差异。公共卫生救援：气味在唤起过去事件的记忆方面是强烈的线索，并在我们对风味的感知中发挥着重要作用，这对我们的生活质量产生了重大贡献。有趣的是，新生儿哺乳动物（包括人类）使用嗅觉信息形成强大的母体附着。这种嗅觉“印迹”到产妇气味对于哺乳和动物的生存至关重要。似乎与其他感觉系统相比，气味信息的皮质处理在出生时既有功能又必要。但是，在这个强大而重要的感觉系统中皮质电路的功能特性尚不清楚。通过阐明气味代表的突触机制，我希望能够深入了解嗅觉信息皮质处理的基本原理。