How Inhibition Shapes Neuronal and Behavioral Responses to Auditory Stimuli
抑制如何塑造神经元和行为对听觉刺激的反应
基本信息
- 批准号:7918851
- 负责人:
- 金额:$ 5.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-08-16 至 2012-08-15
- 项目状态:已结题
- 来源:
- 关键词:AccountingAffectAlbuminsAnimalsAnxietyAuditoryAuditory areaAutistic DisorderBehaviorBehavioralBrainBrain DiseasesCalcium-Binding ProteinsCellsCerebral cortexComplexDendritesDevelopmentDiseaseDistalEpilepsyFire - disastersFrequenciesGenesGoalsHalorhodopsinsHandIndividualInjection of therapeutic agentInterneuronsIon ChannelLightLinkMediatingMental disordersMusNeurologicNeuronsOpticsParvalbuminsPatternPerceptionPhysiologicalPlayPopulationProcessPropertyProteinsPumpResearchRoleSchizophreniaShapesStimulusSynapsesSystemTechnologyTestingTrainingTransgenic MiceTransgenic OrganismsViralVirusWorkauditory stimulusawakecell typedriving behaviorinterestmillisecondneurophysiologyneuroregulationpostsynapticpromoterpublic health relevancereceptive fieldrecombinaserelating to nervous systemresearch studyresponsesoundsynaptic inhibitiontherapeutic development
项目摘要
DESCRIPTION (provided by candidate): The goal of this proposal is to investigate how inhibitory interneurons shape the response properties of cortical projection neurons. The great diversity of interneurons suggests that different subtypes play distinct roles in cortical processing. In addition, abnormal inhibitory circuitry may underlie several neurological and psychiatric disorders, such as epilepsy, schizophrenia, autism, and anxiety. However, thus far it has been difficult to specifically target and manipulate individual interneuronal classes. Recently, the use of cell-type-specific promoters has made it possible to express genes of interest in genetically-delimited groups of cells. I propose to use this technology, in conjunction with optical control of neural activity, to examine the function of specific interneuronal subtypes: those that express parvalbumin (PV+), and those that do not (PV-). My central hypothesis is that PV+ interneurons mediate fast sound-evoked synaptic inhibition, whereas PV- interneurons play a role in dendritic integration and plasticity. I will use Cre/LoxP technology to target the light-sensitive proteins channelrhodopsin-2 (ChR2) and halorhodopsin (Halo) to PV+ and PV- interneurons in auditory cortex, in separate populations of transgenic Cre driver mice, with viral delivery of loxP constructs. ChR2 will be used to optically "tag" PV+ and PV- cells during physiological recordings, allowing me to characterize and compare their response properties. In a separate set of experiments, I will use Halo to selectively silence either PV+ or PV- cells, and observe how this affects sound-evoked activity in auditory cortex in awake mice. When PV+ cells are silenced, I expect auditory responses to be more sustained, less sparse, and less temporally precise. The silencing of PV- interneurons may affect synaptic summation and plasticity. Finally, mice expressing Halo will be trained on auditory tasks, and I will investigate how silencing PV+ o PV- interneurons affects auditory-driven behaviors. PUBLIC HEALTH RELEVANCE: better understanding of how different types of neurons work together will shed light on what can go wrong when brain circuits do not function properly. In particular, disorders such as epilepsy, schizophrenia, autism, and anxiety are thought to involve abnormalities of inhibitory networks in the cerebral cortex. Exploring the link between neural activity, perception, and behavior may guide the development of therapeutic strategies for a variety of brain disorders.
描述(由候选人提供):本提案的目标是研究抑制性中间神经元如何塑造皮质投射神经元的反应特性。中间神经元的巨大多样性表明,不同的亚型在皮层处理中发挥不同的作用。此外,异常的抑制回路可能是几种神经和精神疾病的基础,如癫痫、精神分裂症、自闭症和焦虑症。然而,到目前为止,很难特异性地靶向和操纵单个的中间神经元类。最近,细胞类型特异性启动子的使用使得在遗传上限定的细胞组中表达感兴趣的基因成为可能。我建议使用这种技术,结合光学控制的神经活动,检查特定的interneuronal亚型的功能:那些表达小白蛋白(PV+),和那些不(PV-)。我的中心假设是PV+中间神经元介导快速声音诱发的突触抑制,而PV-中间神经元在树突整合和可塑性中发挥作用。我将使用Cre/LoxP技术将光敏蛋白通道视紫红质-2(ChR 2)和盐视紫红质(Halo)靶向听觉皮层中的PV+和PV-中间神经元,在不同的转基因Cre驱动小鼠群体中,用病毒递送loxP构建体。ChR 2将用于在生理记录期间光学“标记”PV+和PV-细胞,使我能够表征和比较它们的响应特性。在另一组实验中,我将使用Halo选择性地沉默PV+或PV-细胞,并观察这如何影响清醒小鼠听觉皮层的声音诱发活动。当PV+细胞沉默时,我预计听觉反应会更持久,更稀疏,时间上更不精确。PV-中间神经元的沉默可能影响突触的总和和可塑性。最后,表达Halo的小鼠将接受听觉任务的训练,我将研究沉默PV+ o PV-中间神经元如何影响听觉驱动的行为。公共卫生相关性:更好地了解不同类型的神经元如何协同工作,将有助于了解当大脑回路不能正常工作时可能出现的问题。特别是,癫痫、精神分裂症、自闭症和焦虑症等疾病被认为涉及大脑皮层中抑制网络的异常。探索神经活动,感知和行为之间的联系可能会指导各种大脑疾病的治疗策略的发展。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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KATHARINE BORGES其他文献
KATHARINE BORGES的其他文献
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{{ truncateString('KATHARINE BORGES', 18)}}的其他基金
How Inhibition Shapes Neuronal and Behavioral Responses to Auditory Stimuli
抑制如何塑造神经元和行为对听觉刺激的反应
- 批准号:
8119079 - 财政年份:2009
- 资助金额:
$ 5.22万 - 项目类别:
How Inhibition Shapes Neuronal and Behavioral Responses to Auditory Stimuli
抑制如何塑造神经元和行为对听觉刺激的反应
- 批准号:
7674943 - 财政年份:2009
- 资助金额:
$ 5.22万 - 项目类别:
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