Experience Dependent Neocortical Development

经验依赖性新皮质发育

• 批准号: 6906429
• 负责人: Daniel J. Simons
• 金额: $ 24.65万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6906429
• 关键词: axon; biological signal transduction; dendrites; developmental neurobiology; experience; glutamate transporter; histochemistry /cytochemistry; neocortex; neural conduction; neural information processing; neural transmission; neurons; somesthetic sensory cortex; synapses; touch; vibrissae; voltage /patch clamp

DESCRIPTION (provided by applicant): The long-term goal of our research is to understand how experience influences the organization and development of cortical microcircuits Of particular interest is how neonatal tactile experience influences whisker-related barrels in the rat somatosensory cortex. Our previous studies demonstrate that normal tactile experience is essential for the establishment of normal response properties of cortical barrel neurons. Trimming whiskers for the first few postnatal weeks leads to increased excitability of barrel neurons and to a robust and permanent enlargement of their receptive fields. These changes are not, however, accompanied by changes in the topographic pattern or overall morphology of barrels. Instead, available evidence indicates that these physiological abnormalities reflect alterations in local excitatory circuits within individual barrels.The proposed research plan will investigate in detail the development of cortical microcircuits and their alteration by abnormal tactile experience. The research is based on the premise that individual barrels are composed of modular units, and it is at the level of these microcircuits that neonatal experience exerts its influence. These microcircuits are now amenable to analysis using modern cellular-based anatomical and physiological techniques.Experiments are designed to investigate, in normal and whisker-trimmed rats, how cortical microcircuits become matched structurally and functionally to their afferent inputs. Specifically, we will examine in detail 1) the arborization pattern of individual thalamocortical axons, 2) the spatial pattern of locally recurrent intra-barrel connections, and 3) the strength of excitatory synaptic transmission onto individual barrel neurons.Results of the proposed research will provide insight into developmental mechanisms that organize local cortical circuits. By extending, to the somatosensory cortex, important findings from investigations of the visual system, the anticipated results will contribute directly to the identification of general principles of activity-dependent processes underlying cortical development. An understanding of these principles and the cellular mechanisms through which they operate is essential for the eventual diagnosis, treatment and prevention of developmental disorders affecting perception, cognition and other higher cortical functions

描述（由申请人提供）：我们研究的长期目标是了解经验如何影响皮质微电路的组织和发展。特别感兴趣的是新生儿的触觉体验如何影响大鼠体感皮层中与胡须相关的桶。我们之前的研究表明，正常的触觉体验对于建立皮质桶状神经元的正常反应特性至关重要。出生后最初几周修剪胡须会增加桶状神经元的兴奋性，并使其感受野强劲而永久地扩大。然而，这些变化并不伴随着桶的地形图案或整体形态的变化。相反，现有证据表明这些生理异常反映了各个桶内局部兴奋回路的变化。拟议的研究计划将详细调查皮质微回路的发展及其因异常触觉体验而发生的变化。这项研究的前提是，单个桶是由模块化单元组成的，新生儿的经验正是在这些微电路层面上发挥影响。这些微电路现在可以使用现代基于细胞的解剖学和生理学技术进行分析。实验旨在研究正常和胡须修剪的大鼠的皮层微电路如何在结构和功能上与其传入输入相匹配。具体来说，我们将详细检查1）单个丘脑皮层轴突的树状模式，2）局部重复的桶内连接的空间模式，以及3）单个桶状神经元的兴奋性突触传递的强度。拟议研究的结果将为组织局部皮层回路的发育机制提供见解。通过将视觉系统研究的重要发现扩展到体感皮层，预期结果将直接有助于识别皮层发育背后的活动依赖性过程的一般原理。了解这些原理及其运作的细胞机制对于影响感知、认知和其他高级皮质功能的发育障碍的最终诊断、治疗和预防至关重要