Multiplex imaging of neuronal activity and signaling dynamics underlying learning in discrete amygdala circuits of behaving mice.

行为小鼠离散杏仁核回路中神经元活动和信号动态的多重成像是学习的基础。

基本信息

批准号：
10314065
负责人：
Bo LI
金额：
$ 98.83万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-12-15 至 2023-11-30
项目状态：
已结题

项目摘要

PROJECT SUMMARY The amygdala plays a central role in diverse learned behaviors. By integrating the sensory information with stress, punishment, and reward signals, the circuitry within the amygdala is thought to be modified during learning to mediate specific behavioral outcomes. However, the circuit principles governing what is changed and how different types of learning give rise to qualitatively distinct behaviors remains largely unknown. It has been recognized that an important step towards dissecting the circuitry mechanism underlying amygdala- dependent learning is to determine the activities of individual neurons within discrete amygdala circuits before, during, and after a learning task. However, this goal has been challenging to achieve for technical reasons. First, the amygdala is buried deep within the brain, making it difficult to access by imaging methods, such as calcium imaging, which has become a technique of choice for interrogating neuronal action potential activities with cellular resolution over large neuronal populations. Second, the stress and reward signals are in part encoded as neuromodulatory activities, which do not usually result in direct changes in neuronal electrical activities and cannot be measured by calcium imaging or voltage measurements. Measuring neuromodulation in vivo, especially during behavior, remains challenging. Adding to the difficulty, the identity of individual amygdala circuits, as well as where each circuit receives input and where it sends output, are only partially understood. We plan to meet these challenges by integrating the most recent, complementary technological advances from the three co-PIs. In defined behavioral paradigms we will image calcium as a proxy for neuronal firing in the amygdalae of behaving mice by performing two-photon imaging via a tiny GRIN lens (Φ~0.5 mm), which offers optical access to deep brain structures with relatively little damage. Simultaneously through the same GRIN lens, we will image the activity dynamics of the cAMP/protein kinase A (PKA) signaling pathway, which is a common downstream signaling pathway for many neuromodulators, including norepinephrine and dopamine, as readout for stress/reward-induced neuromodulatory signals by using two-photon fluorescence lifetime imaging microscopy. In conjunction, we will perform computation-based anatomical circuitry analyses to dissect novel functional subdivisions of the amygdala, and identify the input-output of each subdivision with cell-type specificity. Based on these techniques, we will systematically map circuits, including previously unknown circuits, within the amygdala and determine how neurons from each circuit are recruited by and contribute to the generation of specific behaviors.

项目摘要杏仁核在潜水员学习的行为中起着核心作用。通过将感官信息与压力，惩罚和奖励信号，杏仁核内的电路被认为在学习调解特定的行为结果。但是，管理什么变更的电路原则以及不同类型的学习如何引起定性不同的行为仍然很大程度上未知。它有我们被认识到，剖析杏仁核基础的电路机制迈出的重要一步依赖的学习是确定以前离散杏仁核中个体神经元的活动，在学习任务之后和之后。但是，出于技术原因，该目标已受到挑战。首先，杏仁核被埋葬在大脑内，使其难以通过成像方法访问，例如钙成像，它已成为询问神经元动作潜在活动的首选技术在大型神经元种群上具有细胞分辨率。其次，压力和奖励信号部分是部分编码为神经调节活动，通常不会导致神经元电的直接变化活动，不能通过钙成像或电压测量来测量。测量神经调节体内，尤其是在行为时期，仍然受到挑战。增加了困难，个人身份 Amygdala电路以及每个电路接收输入以及发送输出的位置，仅是部分理解。我们计划通过整合最新的，完整的技术进步来应对这些挑战这三个共同案件。在定义的行为范例中，我们将钙作为神经元发射的代理通过小小的笑容（φ〜0.5 mm）进行两光片成像，该表演小鼠的杏仁核光学访问深度损坏的深脑结构。同时笑着镜头，我们将成像营地/蛋白激酶A（PKA）信号通路的活性动力学，这是一个许多神经调节剂（包括去甲肾上腺素和多巴胺）的常见下游信号通路，通过使用两光子荧光寿命，作为应力/奖励引起的神经调节信号的读数成像显微镜。结合起来，我们将进行基于计算的解剖电路分析到解剖杏仁核的新型功能细分，并用细胞类型的特异性。基于这些技术，我们将系统地绘制电路，包括以前杏仁核内的未知电路，并确定每个电路中的神经元如何由和有助于产生特定行为。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A Highly Sensitive A-Kinase Activity Reporter for Imaging Neuromodulatory Events in Awake Mice.

DOI：
10.1016/j.neuron.2018.07.020
发表时间：
2018-08-22
期刊：
Neuron
影响因子：
16.2
作者：
Ma L;Jongbloets BC;Xiong WH;Melander JB;Qin M;Lameyer TJ;Harrison MF;Zemelman BV;Mao T;Zhong H
通讯作者：
Zhong H

Opposing Contributions of GABAergic and Glutamatergic Ventral Pallidal Neurons to Motivational Behaviors.

DOI：
10.1016/j.neuron.2019.12.006
发表时间：
2020-03-04
期刊：
Neuron
影响因子：
16.2
作者：
Stephenson-Jones M;Bravo-Rivera C;Ahrens S;Furlan A;Xiao X;Fernandes-Henriques C;Li B
通讯作者：
Li B

Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and parvalbumin-positive interneurons.

DOI：
10.1016/j.celrep.2021.109972
发表时间：
2021-11-09
期刊：
Cell reports
影响因子：
8.8
作者：
Melander JB;Nayebi A;Jongbloets BC;Fortin DA;Qin M;Ganguli S;Mao T;Zhong H
通讯作者：
Zhong H

Genetically encoded sensors towards imaging cAMP and PKA activity in vivo.

DOI：
10.1016/j.jneumeth.2021.109298
发表时间：
2021-10-01
期刊：
Journal of neuroscience methods
影响因子：
3
作者：
Massengill CI;Day-Cooney J;Mao T;Zhong H
通讯作者：
Zhong H

A Genetically Defined Compartmentalized Striatal Direct Pathway for Negative Reinforcement.

DOI：
10.1016/j.cell.2020.08.032
发表时间：
2020-10-01
期刊：
Cell
影响因子：
64.5
作者：
Xiao X;Deng H;Furlan A;Yang T;Zhang X;Hwang GR;Tucciarone J;Wu P;He M;Palaniswamy R;Ramakrishnan C;Ritola K;Hantman A;Deisseroth K;Osten P;Huang ZJ;Li B
通讯作者：
Li B