Supporting Online Material Materials and Methods Som Text Figs. S1 to S5 Tables S1 to S3 References Neuronal Competition and Selection during Memory Formation-猫眼课题宝

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A. Pearson;B. J. Johnson;C. Wilmot;D. Ohlendorf;Jin-Hee Han;S. Kushner;A. Yiu;C. J. Cole;Alcino J. Silva;S. Josselyn

他们的指导和关键的讨论过程中，这项工作，和J。没有数据收集方面的技术援助。GM 24689。我们非常感谢劳伦斯伯克利实验室先进光源（ALS）的光束时间和X射线数据收集的帮助，以及明尼苏达州超级计算研究所的设施和计算机支持。坐标已作为条目2 IG 9（全长酶）和2 IGA（与4 NC和O 2反应的酶）保存在蛋白质数据库（PDB）[www.rcsb.org/pdb]中。神经元之间的竞争对于在发育过程中完善神经回路是必要的，并且对于选择参与成年大脑中编码记忆的神经元可能很重要。为了研究记忆形成过程中的神经元竞争，我们对小鼠进行了实验，在这些实验中，我们操纵了CREB（腺苷3 ′，5 ′-单磷酸反应元件结合蛋白）在神经元亚群中的功能。CREB功能的变化影响了个体杏仁核外侧核神经元被招募到恐惧记忆痕迹中的概率。我们的研究结果表明，一个竞争性模型的基础记忆的形成，其中合格的神经元被选择参与记忆痕迹作为其相对CREB活性的函数在学习的时候。竞争是许多生物系统的基本属性，并在个体元素之间产生选择性压力。例如，双侧单眼神经输入之间的竞争介导了眼优势可塑性（1，2）。转录因子CREB（腺苷3 ′，5 ′-单磷酸反应元件结合蛋白）与发育中的大脑中的这种竞争有关（3，4）。只有一部分合格的神经元参与给定的记忆（5-8），这一发现表明神经元之间的竞争也可能是成年大脑可塑性的基础。听觉条件性恐惧记忆需要外侧杏仁核（LA）的可塑性（7，9-11）。虽然约70%的LA神经元接受必要的感觉输入，但只有四分之一的神经元表现出听觉恐惧条件反射诱导的可塑性（6，7）。我们发现，在听觉恐惧条件反射后，相似比例的LA细胞显示出CREB激活（Ser 133磷酸化）（图1A），这表明CREB在决定哪些神经元被招募到恐惧记忆痕迹中的作用。为了检验该结果，我们通过显微注射表达与绿色荧光蛋白（GFP）融合的内源性或显性阴性CREB（分别为CREB WT和CREB S133 A）的复制缺陷型单纯疱疹病毒载体，在LA神经元的类似部分中操纵CREB功能（12）。为了最大限度地提高神经元之间CREB功能的相对差异，我们首先在一个子集中增加CREB水平。

for their guidance and critical discussions during the course of this work, and J. C. Nix for technical assistance in data collection. GM24689. We are grateful for beam time and assistance with x-ray data collection at the Lawrence Berkeley Laboratory Advanced Light Source (ALS), and for facilities and computer support from the Minnesota Supercomputing Institute. Coordinates have been deposited in the Protein Data Bank (PDB) [www.rcsb.org/pdb] as entries 2IG9 (full-length enzyme) and 2IGA (enzyme reacted with 4NC and O 2). Competition between neurons is necessary for refining neural circuits during development and may be important for selecting the neurons that participate in encoding memories in the adult brain. To examine neuronal competition during memory formation, we conducted experiments with mice in which we manipulated the function of CREB (adenosine 3´,5´-monophosphate response element–binding protein) in subsets of neurons. Changes in CREB function influenced the probability that individual lateral amygdala neurons were recruited into a fear memory trace. Our results suggest a competitive model underlying memory formation, in which eligible neurons are selected to participate in a memory trace as a function of their relative CREB activity at the time of learning. C ompetition is a fundamental property of many biological systems and creates selective pressure between individual elements. For example, competition between bilateral monocular neural inputs mediates ocu-lar dominance plasticity (1, 2). The transcription factor CREB (adenosine 3´,5´-monophosphate response element–binding protein) has been implicated in this competition in the developing brain (3, 4). The finding that only a portion of eligible neurons participate in a given memory (5–8) suggests that competition between neurons may also underlie plasticity in adult brain. Plasticity within the lateral amygdala (LA) is required for auditory conditioned-fear memories (7, 9–11). Although ~70% of LA neurons receive the necessary sensory input, only one-quarter exhibit auditory fear conditioning–induced plasticity (6, 7). We found that a similar proportion of LA cells show activated CREB (phosphoryl-ation at Ser 133) after auditory fear conditioning (Fig. 1A), which suggests a role for CREB in determining which neurons are recruited into the fear memory trace. To examine this result, we manipulated CREB function in a similar portion of LA neurons by microinjecting replication-defective herpes simplex viral vectors expressing endogenous or dominant-negative CREB (CREB WT and CREB S133A , respectively) fused with green fluorescent protein (GFP) (12). To maximize the relative difference in CREB function between neurons, we first increased CREB levels in a subset …

Supporting Online Material Materials and Methods Som Text Figs. S1 to S5 Tables S1 to S3 References Neuronal Competition and Selection during Memory Formation

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