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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：
9217633
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/9217633
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 Interneurons Knowledge Label Lateral Learning Mediating Microscopy Monitor Mus Neurons Neurosciences Odors Olfactory Cortex Olfactory Learning Olfactory Pathways Output Pattern Performance Pharmacology Recurrence Research Reversal Learning Rewards Role Scanning Sensory Signal Transduction Specificity Stimulus Synapses System Techniques Testing Training Variant awake base expectation experience experimental study feeding granule cell information processing learned behavior memory recall mitral cell multiphoton imaging multisensory nervous system disorder olfactory bulb optical imaging optogenetics piriform cortex prevent public health relevance relating to nervous system 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.