Circuit Basis of Decision Making Across the Lifespan

这项提案旨在多伦多斯卡伯勒大学(UTSC)实施帧投影独立光纤测光(FIP)，这是一项突破性的新技术。FIP是一种钙成像技术，它允许同时记录多个大脑区域的神经元活动。这项技术于去年首次发表，目前仅在世界上少数几个实验室使用。FIP将在UTSC的两个研究实验室实施，以研究大脑回路如何支持小鼠和大鼠发育过程中的决策。这项新技术将在两个方面显著推进申请者的研究计划。首先，FIP在为测量活体行为期间相互连接的大脑区域的相对神经元活动水平提供目标特异性和时间精确度方面是独一无二的，这是现有技术迄今无法实现的。其次，FIP可以与系统神经科学中的另一项尖端技术--活体光遗传学相结合，以操纵和验证行为动物的神经元活动。FIP为光遗传操作增加了另一个维度，因为它能够对光刺激的影响进行精确的在线监测，允许刺激参数微调到自然的生理活动水平。这些功能结合在一起，将填补申请者研究中的一个重大空白，该研究目前缺乏测量行为动物的电路动力学的能力，以及调整光遗传刺激方案以模拟自然主义行为参与的活动水平的能力。总体而言，这项技术的实施是一个及时的机会，使UTSC成为安大略省唯一拥有FIP的机构(在加拿大排名第二)，提供(I)为HQP提供独特和高度先进的培训机会，(Ii)改善HQP的招聘工作，(Iii)进一步提高我们研究的国际知名度，(Iv)促进多伦多大学内外的新颖合作。

This proposal aims to implement frame-projected independent-fiber photometry (FIP), a groundbreaking novel technology, at the University of Toronto Scarborough (UTSC). FIP is a calcium imaging technique, which allows the simultaneous recording of neuronal activity across multiple brain regions. This technology was first published last year, and is present in only a handful of labs in the world. FIP will be implemented in two research labs at UTSC to study how brain circuits support decision making across development in mice and rats. This novel technology will significantly advance the applicants’ research programs in two ways. First, FIP is unique in providing the target specificity and time precision for the measuring of the relative neuronal activity levels across interconnected brain regions during live behaviour, something that has been hitherto unachievable with existing techniques. Second, FIP can be combined with another cutting-edge technique in systems neuroscience, in vivo optogenetics, to manipulate and validate neuronal activity in behaving animals. FIP adds another dimension to optogenetic manipulations as it enables precise, online monitoring of the effects of optical stimulation, allowing the stimulation parameters to be fine-tuned to naturalistic, physiological activity levels. Combined, these features will fill a major gap in the applicants’ research, which currently lacks the ability to measure circuit dynamics in behaving animals, and to adjust optogenetic stimulation protocols to mimic activity levels engaged by naturalistic behaviour. Overall, implementation of this technology constitutes a timely opportunity to make UTSC the only institution with FIP in Ontario (and second in Canada), offering (i) unique and highly advanced training opportunities for HQP, (ii) improving HQP recruitment efforts, to (iii) further increase the international profile of our research and (iv) foster novel collaborations both within, and outside of the University of Toronto.