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CRCNS: Multiple Time Scale Memory Consolidation in Neural Networks

CRCNS：神经网络中的多时间尺度内存整合

基本信息

批准号：
10468270
负责人：
Stefano Fusi
金额：
$ 39.6万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-11 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10468270
关键词：
Address Age Animal Experiments Animal Welfare Animals Area Biological Brain Breeding Categories Cervical Code Complex Computer Models Coupled Data Data Analyses Development Dislocations Distress Electronic Mail Electrophysiology (science)Elements Ensure Euthanasia Excision Exhibits Exposure to Failure Female Goals House mice Ice Incubators Individual Injections Injury Joints Laws Lead Learning Long-Term Depression Machine Learning Manuscripts Memory Metaplasia Methods Microscope Modeling Modification Molecular Monitor Motor Mus Neurons Neurosciences Newborn Infant Optical Methods Optics Pain Partner in relationship Postdoctoral Fellow Preparation Procedures Process Protocols documentation Pyramidal Cells Rhodopsin Sensory Series Societies Stimulus Stream Subway Synapses Synaptic plasticity System Techniques Time Transgenic Mice Transgenic Organisms Trees Universities Variant Viral Visualization Walking Weaning Wild Type Mouse artificial neural network base data sharing density design experience experimental study forgetting formycin triphosphate graduate student learning community male meetings member memory consolidation millisecond neural network offspring portability posters postnatal preservation prevent pup sex success theories voltage

项目摘要

Detailed description of the proposed use of the animals, including species, strains, ages, sex, and number to be used; Dissociated, primary cultures will be prepared from the cortex of new born mice of either sex (mus musculus, Postnatal day 0-1). These experiments will be performed using pups obtained from Vglut1-IRES2-Cre strains mated with Floxopatch (Lou et al., 2016) strains so that pyramidal cells will express channel rhodopsin CheRiff and voltage indicator QuasR2. Up to 5 cultures can be grown, which can be used for 5 experiments. Justification for the use of animals, choice of species, and numbers to be used; Description of procedures for minimizing discomfort, distress, pain, and injury; and Method of euthanasia and the reasons for its selection. Transgenic mice (category C) will be used because the experiments rely on the expression of CheRiff and QuasR2 for optical stimulation/recording. There are no alternative species. All experiments are terminal. Newborn mice will be cooled in ice prior to cervical dislocation and excision of the brain for culture preparation. All procedures are in accordance with guideleines of the NYU Animal Welfare Committee. The estimated number of animals below ensure that we have a continuous supply of cultures to perform experiments on a daily basis. Based on our experience in the past 3 years, each postnatal day 0-1 (P0-P1) mouse will generate at least 5 culture preparations. A viable culture will have a have a high density of neurons that express the Floxopatch construct, which varies from mouse to mouse. Thus, if one culture is not viable, all cultures derived from that mouse are also unusable. The success rate is approximately 50%. Because cultures can be made only form P0-1 day old mice and because it is not possible to determine whether expression is sufficient until the day of the experiment 2-3 weeks later, we will need to make 2 sets of cultures per week. Thus, we will need to maintain 2 breeding pairs per week or 8 breeding pairs per month to have a continuous supply of cultures. The breeding pairs will either consist of wildtype mice (for viral injection) or Vglut1-IRES2-Cre - Gt(ROSA)26Sor (floxopatch) mice. Breeding pairs will be replaced every six months. Total animals for experiments: 32 mice/year (=16 mice (8 breeding pairs) x 2/year replacement of breeding pairs). To maintain the 3 lines, 2 males and 2 females each of Vglut1-IRES2-Cre, Gt(ROSA)26Sor, and wildtype mice will be kept in separate cages (4+4+4=12 mice total). Every 6 months (twice per year), the mice of each type will be bred. From their offsprings, 4 males and 4 females from each line will be weaned and kept in separated cages as above (4+ 4 + 4 = 12) and the 4 original breeding pairs (12 mice) euthanized. Overall, 24 mice/year will be used to maintain the lines. Total mice/year: 56 (=24 mice/year to maintain lines + 32 mice/year for experiment). Total mice over 3 years = 168 mice. Reference Lou et al., (2016) Genetically Targeted All-Optical Electrophysiology with a Transgenic Cre-Dependent Optopatch Mouse, J. Neurosci. 36:11059-73 1 53 Results from previous support from CRCNS The P.I. and co-P.I. have not received previous CRCNS support Coordination Plan Division of labor The P.I. (A. Reyes) and his group at NYU will perform the experiments and analyses detailed in Aims 1 and 2 of this proposal. The co-P.I (S. Fusi) and his group at Columbia University will be responsible for the development of the theory and computational models that will incorporate the experimental data. Data Sharing between NYU and Columbia groups: Analyzed data, model codes, and manuscripts in progress will be disseminated between the groups via Google drive. All members of the Fusi and Reyes groups will have access upon email request. Larger, raw data will be stored on local servers and accessible via FTP. Coordination between NYU and Columbia University Because NYU and Columbia are easily acces- sible by subway, we will have monthly joint lab meetings, alternating between NYU and Columbia. Graduate students and postdoctoral fellows will be encouraged to submit joint poster presentations or talks to annual meetings such as Cosyne and Society for Neuroscience Meetings. 16 54

拟定动物用途的详细描述，包括物种、菌株、年龄、性别和使用数量；分离的原代培养物将从新生小鼠的皮质中制备性别（肌肉，产后 0-1 天）。这些实验将使用从与 Floxopatch 交配的 Vglut1-IRES2-Cre 菌株中获得的幼崽（Lou 等人，2016）使锥体细胞表达通道视紫红质 CheRiff 和电压指标 QuasR2。最多可培养 5 个培养物，可用于 5 次实验。使用动物的理由、物种的选择和使用的数量；描述尽量减少不适、痛苦、疼痛和伤害的程序；安乐死的方法及其选择的原因。将使用转基因小鼠（C 类），因为实验依赖于用于光刺激/记录的 CheRiff 和 QuasR2 的表达。没有替代物种。所有的实验都是终点。新生小鼠在宫颈切除前将被冰冷大脑脱位和切除以进行培养准备。所有手续都在根据纽约大学动物福利委员会的指导方针。以下估计的动物数量确保我们有持续的供应每天进行实验的培养物。根据我们过去3年的经验年，出生后每一天 0-1 (P0-P1) 小鼠将产生至少 5 个培养物准备工作。一个可行的培养物将具有高密度的神经元，这些神经元表达 Floxopatch 构建体，因小鼠而异。因此，如果一种文化不可行，所有源自该小鼠的培养物也无法使用。成功率是大约50%。因为只能从 P0-1 日龄的小鼠中进行培养，并且因为直到当天才能确定表达是否充分实验2-3周后，我们需要每周进行2组培养。因此，我们需要每周维持 2 对繁殖对或每月 8 对繁殖对拥有源源不断的文化供应。育种对将由野生型组成小鼠（用于病毒注射）或 Vglut1-IRES2-Cre - Gt(ROSA)26Sor (floxopatch) 小鼠。繁殖对每六个月更换一次。实验动物总数：32 只小鼠/年（=16 只小鼠（8 个繁殖对）x 2/年更换育种对）。为了维持 3 个品系，每个 Vglut1-IRES2-Cre 2 个雄性和 2 个雌性， Gt(ROSA)26Sor，和野生型小鼠将被关在单独的笼子中（4+4+4=12只小鼠全部的）。每 6 个月（每年两次），每种类型的小鼠都会被繁殖。来自他们的后代，每系 4 只雄性和 4 只雌性将断奶并分开饲养上述笼子(4+4+4=12)和4对原始繁殖对(12只小鼠)被安乐死。总体而言，每年将使用 24 只小鼠来维持品系。小鼠总数/年：56 只（=24 只小鼠/年用于维持系+ 32 只小鼠/年用于实验）。 3 年以上的小鼠总数 = 168 只小鼠。参考 Lou 等人，（2016）转基因靶向全光电生理学 Cre 依赖性 Optopatch 小鼠，J. Neurosci。 36:11059-73 1 53 CRCNS 先前支持的结果 P.I.和共同 P.I.之前没有收到过 CRCNS 支持协调计划分工（A. Reyes）和他在纽约大学的团队将进行实验和分析本提案的目标 1 和 2 中有详细说明。哥伦比亚大学的联合 P.I (S. Fusi) 和他的团队将负责理论和计算模型的开发，其中将结合实验数据。纽约大学和哥伦比亚大学小组之间的数据共享：分析数据、模型代码和手稿正在进行的工作将通过 Google Drive 在各小组之间传播。福斯和雷耶斯的所有成员团体可以根据电子邮件请求进行访问。更大的原始数据将存储在本地服务器上并可访问通过FTP。纽约大学和哥伦比亚大学之间的协调因为纽约大学和哥伦比亚大学交通便利乘坐地铁，我们每月都会举行联合实验室会议，轮流在纽约大学和哥伦比亚大学举行。毕业将鼓励学生和博士后研究员向年度会议提交联合海报展示或演讲 Cosyne 和神经科学学会会议等会议。 16 54