Understanding the roles of cortico-bulbar feedback in odor identification

了解皮质球反馈在气味识别中的作用

基本信息

批准号：
9106954
负责人：
Dinu Florentin ALBEANU
金额：
$ 40.8万
依托单位：
COLD SPRING HARBOR LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-09 至 2021-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9106954
关键词：
Accelerometer Affect Animals Area Attention Axon Behavior Behavior monitoring Behavioral Binding Brain Brain region Calcium Signaling Cells Chronic Code Computer Simulation Cytoplasmic Granules Data Discrimination Environment Feedback Fiber Glutamates Head Human Image Interneurons Knowledge Label Lateral Learning Mediating Microscopy Monitor Mus Neurons Neurosciences Odors Olfactory Cortex Olfactory Learning Olfactory Pathways Output Pattern Performance Process Recurrence Research Reversal Learning Rewards Role Scanning Sensory Sensory Process Signal Transduction Specificity Stimulus Synapses System Techniques Testing Training Variant Work awake base expectation experience feeding granule cell information processing learned behavior memory recall mitral cell multisensory nervous system disorder olfactory bulb optical imaging optogenetics piriform cortex prevent public health relevance relating to nervous system research study response sensory discrimination sensory input sensory stimulus tool

项目摘要

DESCRIPTION (provided by applicant): Sensory circuits integrate inputs from the environment, as well as feedback signals from higher brain regions. The interplay of feed-forward and feedback signals is proposed to be fundamental for processing behaviorally relevant information related to expectation, reward, attention and action, during learning and memory recall. Though rich glutamatergic cortical feedback projections innervate inhibitory interneurons in all olfactory bulb layers, to date their specific dynamics and contribution to olfactory processing remains largely unknown. Using multiphoton imaging of GCaMP5 signals in awake head-fixed mice, the Albeanu group recently established that, in response to a diverse panel of odors and across concentrations, corticalbulbar feedback is sparse, odor selective, long-lasting post stimulus offset, spatially diverse and carried by two largely independent bouton/fiber types. Here, the PI, Albeanu, will test the central hypothesis that, in awake mice, cortical feedback contextually modulates inhibitory micro-circuits in the olfactory bulb to enhance discriminability of behaviorally relevant odors. Mechanistically, Dr. Albeanu's group proposes that cortico-bulbar projections respond specifically to stimulus identity and concentration by increasing the odor responsiveness of inhibitory interneurons and de-correlating the responses of mitral/tufted cells to different odors, and that these feedback effect are tuned by odor learning. Aim 1: Suppress olfactory cortex activity pharmacologically or optogenetically, while monitoring its effects on the dynamics of two classes of interneurons in the bulb - the granule cells, and the deep short axon - on the mitral cells, the bulb outputs via multiphoton imaging. To achieve further specificity, suppress cortical feedback boutons locally in the bulb while monitoring their targets in the bulb. Aim 2: Investigate how cortical feedback changes pre- versus post-acquisition of olfactory discrimination tasks and multisensory reversal learning paradigms. Train head-fixed mice in simple olfactory go-no go and two forced choice tasks, monitor the cortical feedback, and compare the correlations between learned and unfamiliar odors before and after training, as well as responses to the same sensory stimuli under different contingencies. Aim 3: Assess the effects of cortical feedback suppression on behavioral performance in olfactory sensory discrimination and reverse learning tasks, and on the responses of granule cells, deep short axon cells and mitral cells via monitoring GCaMP6 signals. The following hypotheses will be tested: (1) cortical feedback binds recent activity patterns in the piriform cortex to ongoing sensory inputs in the olfactory bulb and modulates mitral cell representations to facilitate the identification of behaviorally relevant odors, and (2 cortical feedback broadcasts contextual signals that are used by the olfactory bulb output to help identify rewarded stimuli.

描述（由适用提供）：感官电路集成了来自环境的输入，以及来自较高大脑区域的反馈信号。提议在学习和记忆回忆期间，馈送和反馈信号的相互作用对于处理与期望，奖励，注意力和行动相关的行为相关信息至关重要。尽管富含谷氨酸的皮质反馈投影支配所有嗅球层中的抑制性中间神经元，但迄今为止，它们对嗅觉加工的具体动力和贡献仍然很大程度上是未知的。 Albeanu Group使用醒着头部固定的小鼠中GCAMP5信号的多型子成像，最近确定，为了响应潜水员的气味和浓度，皮质纤维反馈是稀疏，气味选择性的，持久的刺激后偏移，空间上延伸的刺激后，并由两种独立的独立bouton/fiber类型携带。在这里，PI Albeanu将检验以下中心假设：在清醒的小鼠中，皮质反馈在嗅球中抑制了抑制微电路，以增强行为相关气味的可区分性。从机械上讲，Albeanu博士的小组提出的提案是，Cortico-Bulbar项目通过增加抑制性中间神经元的气味反应性并消除二尖瓣/簇状细胞对不同气味的反应，并通过ODOR学习调节这些反馈效应。 AIM 1：从药理学或光遗传学上抑制嗅觉皮层活性，同时监测其对灯泡中两类中间神经元的动力学的影响 - 颗粒细胞 - 颗粒细胞和深短轴突 - 在二尖瓣上，灯泡通过多霍特成像进行灯泡输出。为了获得进一步的特异性，请在监测灯泡中的靶标时抑制灯泡本地的皮质反馈胸子。 AIM 2：研究皮质反馈如何改变嗅觉歧视任务和多感官逆转学习范式的事后事后。训练简单的嗅觉中的固定小鼠，不执行和两项强制选择任务，监视皮质反馈，并比较训练前和之后学习和不熟悉的气味之间的相关性，以及在不同意外情况下对相同的感官刺激的响应。目标3：通过监测GCAMP6信号，评估嗅觉感觉歧视和反向学习任务中的皮质反馈抑制对嗅觉感觉歧视和反向学习任务的行为性能的影响，以及颗粒细胞，深短轴突细胞和二尖瓣细胞的响应。 The following hypotheses will be tested: (1) cortical feedback binds recent activity patterns in the piriform cortex to ongoing sensory inputs in the olfactory bulb and modulates mitral cell representations to facilitate the identification of behaviorally relevant odors, and (2 cortical feedback broadcasts contextual signals that are used by the olfactory bulb output to help identify rewarded stimuli.