Connections of Inhibitory Cortical Neurons

抑制性皮质神经元的连接

基本信息

批准号：
8324208
负责人：
EDWARD M CALLAWAY
金额：
$ 47.63万
依托单位：
SALK INSTITUTE FOR BIOLOGICAL STUDIES
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-08-25 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8324208
关键词：
Apical Attention Autistic Disorder Behavioral Biological Assay Brain Cells Cerebral cortex Cholecystokinin Complex Disease Distant Future Goals Health Human Image Infection Injection of therapeutic agent Interneurons Knowledge Label Life Light Literature Methods Molecular Genetics Monitor Mus Myoepithelial cell Nervous System Physiology Nervous system structure Neurons Operating System Optics Output Parvalbumins Population Presynaptic Terminals Property Rabies Rabies virus Relative (related person)Research Role Schizophrenia Slice Somatosensory Cortex Somatostatin Source Specificity Structure Synapses System Technology Testing Vasoactive Intestinal Peptide Viral Whole-Cell Recordings Work adeno-associated viral vector base calretinin cell type design excitatory neuron follow-up hippocampal pyramidal neuron in vivo inhibitory neuron interest neural information processing neuronal cell body novel optogenetics postsynaptic presynaptic promoter research study selective expression tool

项目摘要

DESCRIPTION (provided by applicant): The function of the nervous system is dependent on complex interactions between networks of neurons composed of multiple neuron types. Understanding how these networks function both in health and disease is dependent on understanding the precise connectivity between specific neurons types. It is therefore apparent that, in order to have an adequate understanding of the nervous system, it is necessary to have detailed descriptions of neuronal connectivity with the same level of precision at which these systems operate. The research proposed here is aimed at revealing the detailed connectivity of specific types of inhibitory cortical neurons. A novel Cre-dependent and rabies-based tracing system will be used to reveal the direct monosynaptic connections to neurons in primary somatosensory cortex of five different Cre-driver mouse lines. The intersection of Cre-expression in specific cell groups, with AAV infection and specific promoters, will define specific populations of inhibitory neurons that can be infected with the rabies virus. Transcomplementation and retrograde transsynaptic spread of the rabies virus will reveal the cells, across the entire brain, that make direct connections to the targeted cortical inhibitory neurons. To assess the specificity of local outputs from specific types of inhibitory cortical neurons, similar targeting methods will be used to selectively express channelrhodopsin (ChR2) in specific cell groups. Living brain slices will then be prepared and functional connections assayed by recording intracellularly from potential postsynaptic cell types of interest while "optogenetically" activating the ChR2 positive cells. The results of these experiments will shed light on the feasibility of various hypotheses about the functional roles of particular types of inhibitory cortical neurons and will guide future studies monitoring and manipulating the activity of specific cell types.

描述（由申请人提供）：神经系统的功能取决于由多种神经元类型组成的神经元网络之间的复杂相互作用。了解这些网络在健康和疾病中如何发挥作用取决于了解特定神经元类型之间的精确连接。因此，显然，为了充分了解神经系统，有必要以与这些系统运行相同的精度水平对神经元连接进行详细描述。这里提出的研究旨在揭示特定类型的抑制性皮层神经元的详细连接性。一种新型的 Cre 依赖性和基于狂犬病的追踪系统将用于揭示与五种不同 Cre 驱动小鼠品系的初级体感皮层神经元的直接单突触连接。特定细胞群中 Cre 表达与 AAV 感染和特定启动子的交叉，将定义可以感染狂犬病病毒的特定抑制性神经元群体。狂犬病病毒的反补体和逆行突触传播将揭示整个大脑中与目标皮质抑制神经元直接连接的细胞。为了评估特定类型的抑制性皮层神经元局部输出的特异性，将使用类似的靶向方法在特定细胞群中选择性表达视紫红质通道蛋白（ChR2）。然后将制备活体脑切片，并通过在细胞内记录潜在的感兴趣的突触后细胞类型，同时“光遗传学”激活 ChR2 阳性细胞来分析功能连接。这些实验的结果将揭示有关特定类型抑制性皮层神经元功能作用的各种假设的可行性，并将指导未来监测和操纵特定细胞类型活动的研究。