Functional Dissection of New Retinal Circuits

新视网膜回路的功能解剖

基本信息

批准号：
9010269
负责人：
Z JIMMY ZHOU
金额：
$ 41.75万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-01 至 2018-11-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The goal of this proposal is to dissect and understand functional neural circuits in the mammalian retina, with a focus on the newly identified glutamatergic amacrine cell (GAC) circuit. The proposed studies are based on our recent finding of unconventional glutamatergic synaptic transmission from GACs to specific ganglion cell types (Lee et al. Neuron, 2014). This finding suggests intriguing neuronal circuits of GACs and new forms of visual computation in the inner retina. Although little is currently known about the GAC circuitry, several distinct advantages of the GAC system in the mouse retina present a rare opportunity for us to investigate (1) how a defined amacrine cell type makes functional connections with its upstream input neurons, (2) how this cell type responds to and processes visual inputs, and (3) how this cell type forms synaptic circuits with downstream target neurons and contributes to visual computation in the inner retina. Being an excitatory (and potentially dual excitatory/inhibitory) amacrine cell type, GACs also provide a unique opportunity for us to investigate the possibility of new forms of co-neurotransmission and test new theories of amacrine cell function in the retina. The proposed studies will address the above questions using a combination of electrophysiology, two-photon imaging, optogenetics, and chemogenetics in a powerful wholemount retinal preparation of a transgenic mouse line in which GACs can be specifically identified and genetically manipulated. The ability to integrate these advanced techniques in a set of carefully designed experiments will allow us to obtain detailed physiological, neurochemical, and circuit information about the GAC network at a level unattainable by other experimental approaches. The proposal will pursue three specific aims: (1) understand the cellular and dendritic response properties of GACs, (2) understand the connectivity and the function of the GAC output circuit, and (3) understand the functional inputs from bipolar cell types to GACs. Results from these studies are expected to provide novel insights into both the connectome and the physiology of a novel retinal circuit and shed important light on retinal circuitry and retinal function in health and disease.

描述（由适用提供）：该提案的目的是在哺乳动物视网膜中剖析和理解功能性神经元电路，重点是新鉴定的谷氨酸谷歌疗程（GAC）电路。拟议的研究是基于我们最近发现的非常规谷氨酸能突触从GACS到特定神经节细胞类型的传播（Lee等人Neuron，2014）。这一发现表明，GAC的神经元回路和内部视网膜中的新形式的视觉计算形式。 Although little is currently known about the GAC circuitry, several distinct advantages of the GAC system in the mouse retina present a rare opportunity for us to investigate (1) how a defined amacrine cell type makes functional connections with its upstream input neurons, (2) how this cell type responses to and processes visual inputs, and (3) how this cell type forms synaptic circuits with downstream target neurons and contributes to visual computation in the inner retina.作为一种运动（可能是双重运动/抑制性的）无链氨氨酸细胞类型，GAC还为我们提供了一个独特的机会，为我们研究了新形式的共尿液传递的可能性，并测试视网膜中木氨酸细胞功能的新理论。拟议的研究将使用电生理学，两光子成像，光遗传学和化学遗传学的结合在强大的转基因小鼠系列中解决上述问题，在其中可以特异性地识别出GAC，并经常操纵GAC。将这些先进技术集成到一组精心设计的实验中的能力将使我们能够在其他实验方法无法达到的水平上获得有关GAC网络的详细生理，神经化学和电路信息。该提案将追求三个特定目的：（1）了解GAC的细胞和树突响应特性，（2）了解GAC输出电路的连通性和功能，（3）了解双极单元类型到GAC的功能输入。这些研究的结果预计将提供有关新型视网膜电路的连接组和生理学的新见解，并为视网膜电路和健康和疾病中的残留功能提供了重要的启示。