Biased randomness: a fundamental connectivity mechanism for associative brain centers

偏向随机性：关联大脑中心的基本连接机制

• 批准号: 10204134
• 负责人: Sophie Caron
• 金额: $ 33.36万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10204134
• 关键词: Accounting; Acetates; Address; Anatomy; Animals; Behavior; Behavioral; Biological Process; Brain; Candidate Disease Gene; Cells; Cognitive; Data Set; Drosophila genus; Drosophila melanogaster; Ecology; Environment; Frequencies; Genes; Goals; Individual; Instinct; Interneurons; Learning; Light; Lobe; Logic; Maps; Modeling; Molecular; Mushroom Bodies; Nature; Neurons; Neurosciences; Odors; Outcome; Pattern; Performance; Pheromone; Randomized; Research; Sensory; Social Behavior; Statistical Data Interpretation; Stimulus; Synapses; Techniques; Testing; Work; behavioral response; design; experimental study; geosmin; human disease; insight; learning ability; mathematical model; microbial; predictive modeling; presynaptic; sensory input

SUMMARY Uncovering fundamental mechanisms of neuronal connectivity that enable associative brain centers to learn is an important goal of neuroscience. In the Drosophila melanogaster mushroom body, the constituent Kenyon cells receive input from olfactory projection neurons. Each projection neuron connects to one of the 50 glomeruli in the antennal lobe, the primary olfactory processing center. Our previous work has shown that these connections are random in that there are no sets of glomeruli converging preferentially onto a given Kenyon cell. However, the glomeruli are not represented with equal frequency among Kenyon cell inputs. Certain glomeruli are significantly overrepresented or underrepresented, even though a uniform distribution would be optimal for learning performance. We are proposing to test the idea that this non-uniform distribution, which we termed ‘biased randomness’, serves an important function, namely to predispose the learning ability of an associative brain center towards certain ethologically pertinent stimuli. To test this idea, first, the representation of individual glomeruli will be compared in three different Drosophila species and investigated for correlations to differences in chemosensory ecology (Specific Aim 1). Second, molecular regulators of glomerular representation will be identified in D. melanogaster to manipulate the representation of individual glomeruli and test for effects on olfactory representation in the mushroom body and learning (Specific Aim 2). The research in this proposal has the potential to reveal a fundamental mechanism by which neuronal connectivity is fine-tuned to predispose learning towards particularly pertinent stimuli, thus possibly accounting for cognitive biases. 1

概括 揭示使联想大脑中心能够学习的神经元连接的基本机制是 神经科学的一个重要目标。在果蝇蘑菇体内，成分凯尼恩 (Kenyon) 细胞接收来自嗅觉投射神经元的输入。每个投射神经元连接到 50 个肾小球之一 在触角叶，初级嗅觉处理中心。我们之前的工作表明，这些 连接是随机的，因为没有一组肾小球优先会聚到给定的凯尼恩细胞上。 然而，凯尼恩细胞输入中肾小球的出现频率并不相同。某些肾小球 明显过高或过低，即使均匀分布对于以下情况来说是最佳的： 学习表现。我们建议测试这种非均匀分布的想法，我们称之为 “有偏见的随机性”具有重要的功能，即预先安排联想的学习能力 大脑中枢朝向某些与行为学相关的刺激。为了检验这个想法，首先，个人的代表性 将比较三种不同果蝇物种的肾小球并研究差异的相关性 化学感应生态学（具体目标 1）。其次，肾小球代表性的分子调节剂将是 在黑腹果蝇中鉴定出操纵单个肾小球的表现并测试对 蘑菇体中的嗅觉表征和学习（具体目标 2）。本提案中的研究 有可能揭示一种基本机制，通过该机制微调神经元连接以诱发 针对特别相关的刺激进行学习，从而可能解释认知偏差。 1