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Neural mechanisms of cognitive memory system : Integration of functional magnetic resonance imaging method and molecular / allular approaches

认知记忆系统的神经机制：功能磁共振成像方法与分子/全细胞方法的整合

基本信息

批准号：
07102006
负责人：
MIYASHITA Yasushi
金额：
$ 346.3万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Specially Promoted Research
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 2001
项目状态：
已结题

项目摘要

1. In primates, visual long-term memory of objects is presumably stored in the inferior temporal (IT) cortex. Because brain-derived neurotrophic factor (BDNF) is involved in activity-dependent neural reorganization, we tested the hypothesis that BDNF would be upregulated in IT cortex during formation of visual pair-association memory. To eliminate genetic and cognitive variations between individual animals, we used split-brain monkeys for intra-animal comparison in PCR-based mRNA quantitation. The monkeys learned a pair-association (PA) task using one hemisphere and a control visual task using the other, to balance the amount of visual input. We found that BDNF was upregulated selectively in area 36 of IT cortex during PA learning, but not in areas involved in earlier stages of visual processing. The results suggest that BDNF contributes to reorganization of neural circuits for visual long-term memory formation in the primate (Tokuyama et al. Nature neuroscience 3, 1134-1142, 2000).2. … More Bidirectional signaling between neocortex and limbic cortex has been hypothesized to contribute to the retrieval of long-term memory. We tested this hypothesis by comparing the time courses of perceptual and memory-retrieval signals in two neighboring areas in temporal cortex, area TE (TE) and perirhinal cortex (PRh), while monkeys were performing a visual pair-association task. Perceptual signal reached TE before PRh, confirming its forward propagation. In contrast, memory-retrieval signal appeared earlier in PRh, and TE neurons were then gradually recruited to represent the sought target. A reasonable interpretation of this finding is that the rich backward fiber projections from PRh to TE may underlie the activation of TE neurons that represent a visual object retrieved from long-term memory (Naya, Yoshida ＆ Miyashita, Science 291, 661-664, 2001).3. Functional brain organization of macaque monkeys and humans was directly compared by functional magnetic resonance imaging. Subjects of both species performed a modified Wisconsin Card Sorting Test that required behavioral flexibility in the form of cognitive set shifting. Equivalent visual stimuli and task sequence were used for the two species. We found transient activation related to cognitive set shifting in focal regions of prefrontal cortex in both monkeys and humans. These functional homologs were located in cytoarchitectonically equivalent regions in the posterior part of ventrolateral prefrontal cortex. This comparative imaging provides insights into the evolution of cognition in primates (Nakahara, Hayashi, Konishi ＆ Miyashita, Science 295, 1532-1536, 2002). Less

1.在灵长类动物中，对物体的视觉长期记忆可能储存在下颞叶皮质(IT)。由于脑源性神经营养因子(BDNF)参与了活性依赖的神经重组，我们验证了BDNF在视觉配对联想记忆形成过程中在IT皮质上调的假说。为了消除个体动物之间的遗传和认知差异，我们使用裂脑猴子在基于PCR的mRNA定量中进行动物内比较。猴子使用一个大脑半球学习配对联想(PA)任务，使用另一个大脑半球学习控制视觉任务，以平衡视觉输入量。我们发现，在PA学习过程中，脑源性神经营养因子在大脑IT区36区有选择性地上调，但在视觉加工的早期阶段没有上调。结果表明，BDNF有助于灵长类动物视觉长期记忆形成的神经回路的重组(Tokuyama等人。自然神经科学3,1134-1142,2000)…新皮质和边缘皮质之间更多的双向信号被认为有助于恢复长期记忆。当猴子执行视觉配对联想任务时，我们通过比较颞叶皮质中两个相邻区域TE区(TE)和周边皮质(PRH)的知觉和记忆提取信号的时间进程来检验这一假设。感知信号在PRH前到达TE，确认其正向传播。相反，记忆提取信号在PRH较早出现，然后逐渐招募TE神经元来代表寻找的目标。对这一发现的合理解释是，从PRH到TE的丰富的后向纤维投射可能是TE神经元激活的基础，TE神经元代表从长期记忆中提取的视觉对象(Naya，Yoshida&Miyashita，Science 291,661-664,2001)。通过功能磁共振成像直接比较猕猴和人类的脑功能组织。这两个物种的受试者都进行了修改后的威斯康星卡片分类测试，该测试需要认知集转移形式的行为灵活性。这两个物种都使用了等量的视觉刺激和任务序列。我们在猴子和人类的前额叶皮质的焦点区域发现了与认知集转移相关的短暂激活。这些功能同源物位于前额叶腹外侧皮质后部的细胞构筑等效区。这种比较成像提供了对灵长类动物认知进化的洞察(Nakahara，Hayashi，Konishi&Miyashita，Science 295,1532-1536,2002)。较少