Cell type-specific calcium imaging during hippocampus-dependent memory

海马依赖性记忆过程中的细胞类型特异性钙成像

基本信息

批准号：
8509792
负责人：
LARRY S ZWEIFEL
金额：
$ 18.54万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-13 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8509792
关键词：
Address Adenylate Cyclase Advocate Aging Animals Behavior Behavioral Biochemical Brain region Calcium Calcium Spikes Cells Cognition Cyclic AMP Data Dependovirus Elements Episodic memory Fiber Optics Fluorescence Fright Genetic Goals Hippocampus (Brain)Hour Human Image Imaging Techniques Implant In Situ Individual Intervention Lasers Learning Link Location MAP2K1 gene Maps Mechanics Mediating Memory Memory impairment Mental disorders Methods Molecular Monitor Mus Neurons Neurosciences Neurosciences Research Optics Pattern Pharmacology Phase Population Property Proxy Pyramidal Cells Relative (related person)Reproducibility Research Resolution Retrieval Role Shock Signal Transduction Synapses System Techniques Time Training Transgenic Mice Variant awake base calcium indicator cell type cellular targeting conditioned fear conditioning dentate gyrus experience extracellular genetic discrimination granule cell in vivo information processing inhibitor/antagonist interest long term memory medical schools memory encoding memory recall memory retrieval novel novel strategies peer prevent public health relevance recombinase research study response selective expression way finding

项目摘要

DESCRIPTION (provided by applicant): Evidence from humans and animals indicate a critical role for the hippocampus in the formation of long- term episodic memories. The hippocampus consists of anatomically segregated subregions with a diversity of neuronal types hypothesized to encode different aspects of an experience. Although the molecular mechanisms of activity-dependent plasticity in hippocampal neurons have been intensely scrutinized, we have limited understanding of the activity patterns shown by select neuronal populations during memory encoding, consolidation and recall. Therefore, there is a strong demand to develop new imaging approaches that can interrogate the activity of hippocampal circuits in the context of the behavior that they are thought to support. Because neuronal spikes are associated with large intracellular calcium conductances, calcium indicators can be used as a proxy for neuronal activation. In the proposed research, we will implement the use of fiber optic fluorescence endomicroscopy (FFE) to chronically monitor the activation of defined hippocampal neurons in mice subjected to hippocampus-dependent tasks. A genetically-encoded calcium indicator will be conditionally expressed in transgenic mice selectively expressing Cre recombinase in CA1 pyramidal cells, or in dentate granule cells and CA3 pyramidal cells. Our initial proof-of-principl experiments in fully awake, unrestricted mice advocate the feasibility of this approach for large-population imaging of single-neuron activity. In our first aim, we will optimize the parameters of FFE required to achieve stable, long-term imaging of the different neuronal populations. In our second aim, we will use this method to define the neuronal ensembles that encode contextual- and trace-fear conditioning, two hippocampus-dependent variants of associative memory hypothesized to engage different circuits. Time-lapse experiments will allow comparisons of the activation patterns observed during training, consolidation and recall. Through genetic or pharmacological interventions against each one of these memory phases, we will link the activity of select neurons to cognition. Thus, the proposed research will advance the field by introducing FFE as a novel in vivo approach to study memory mechanisms, and will use this technique to begin to address previously inaccessible questions on the cellular basis of memory.

描述（由申请人提供）：人类和动物的证据表明，海马在形成长期发作记忆中的关键作用。海马由解剖上隔离的子区域组成，这些子区域具有多种神经元类型，该区域被认为编码体验的不同方面。尽管对海马神经元中活性依赖性可塑性的分子机制进行了严格的审查，但在记忆编码，巩固和回忆期间，我们对某些神经元种群所示的活性模式的理解有限。因此，有很大的需求需要开发新的成像方法，可以在他们认为支持的行为的背景下审问海马电路的活动。由于神经元尖峰与大细胞内钙电导有关，因此钙指示剂可以用作神经元激活的代理。在拟议的研究中，我们将实施光纤荧光内部显微镜（FFE）的使用来长期监测受海马依赖性任务的小鼠中定义的海马神经元的激活。遗传编码的钙指示剂将在有条件地表达在CA1锥体细胞中的CRE重组酶的转基因小鼠中，或在齿状颗粒细胞和CA3锥体细胞中。我们在完全清醒的无限制小鼠中进行的初步证明实验提倡这种方法对单神经活性进行大型人口化成像的可行性。在我们的第一个目标中，我们将优化实现不同神经元种群稳定的长期成像所需的FFE参数。在我们的第二个目标中，我们将使用此方法来定义编码上下文和痕量曲调调节的神经元集合，这是两个依赖于关联记忆的海马依赖性变体，该变体假设参与不同的电路。延时实验将允许比较在训练，合并和召回期间观察到的激活模式。通过针对这些记忆阶段的每个记忆阶段的遗传或药理干预措施，我们将选择的神经元的活性与认知。因此，拟议的研究将通过引入FFE作为一种研究记忆机制的新型方法来推进该领域，并将使用该技术开始在记忆的细胞基础上开始解决以前无法访问的问题。