Development of Synaptic Plasticity in Visual Cortex

视觉皮层突触可塑性的发展

• 批准号: 7454189
• 负责人: MICHAEL J FRIEDLANDER
• 金额: $ 32.12万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-04 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7454189
• 关键词: Attention; Calcium; Calcium Channel; Calcium Oscillations; Calcium Signaling; Calcium-Sensing Receptors; Cells; Cerebral cortex; Characteristics; Chemosensitization; Chromosome Pairing; Chronic; Class; Cognitive; Control Animal; Coupled; Dendrites; Dendritic Spines; Development; Event; Experimental Models; Failure; Glutamate Receptor; Goals; Individual; Injury; Kinetics; Lead; Learning; Life; Long-Term Depression; Measures; Mental Depression; Metabotropic Glutamate Receptors; Molecular; N-Methyl-D-Aspartate Receptors; Nature; Neonatal; Neurons; Outcome; Output; Pattern; Performance; Physiologic pulse; Population; Process; Property; Protocols documentation; Pulse taking; Rate; Recording of previous events; Regulation; Retinal; Role; Ruthenium Red; Ryanodine Receptor Calcium Release Channel; Ryanodine Receptors; Shapes; Signal Transduction; Site; Source; Surface; Synapses; Synaptic plasticity; Tetrodotoxin; Thapsigargin; Time; Vision; Visual; Visual Cortex; Visual Perception; XeC compound; area striata; base; biocytin; cell type; computerized data processing; conditioning; cyclopiazonic acid; dark rearing; excitatory neuron; experience; hippocampal pyramidal neuron; inositol-1,4,5-triphosphate receptor; neocortical; neuronal cell body; parallel computing; postnatal; postsynaptic; presynaptic; prevent; research study; response; skills; transmission process; vision development; visual process; visual processing; voltage

DESCRIPTION (provided by applicant): Synapses in the cerebral cortex undergo dynamic alterations in their efficiency throughout life. In particular, the neurons of the primary visual cortex can use such synaptic plasticity to perform parallel computations on aspects of visual processing. Such activity-dependent changes in synaptic signaling have been suggested to contribute to visual perception, cognitive performance, skill-learning, developmental re-organization and refinement of functional visual cortical synaptic networks and adaptive responses after injury. These forms of plasticity undergo dramatic changes in their robustness, modulation by intrinsic and extrinsic factors and underlying molecular processes during postnatal development. However, the developmental regulation of these forms of functional synaptic plasticity has received less attention. We utilize an experimental model of neocortical synaptic plasticity that is based on serial correlations of synaptic input with activation of the postsynaptic neuron to characterize the initial intracellular calcium triggering events that generally lead to long term synaptic potentiation (LTP). Interestingly, in the neonatal visual cortex, when the identical serial correlations are applied to neurons of the same class (layer 2/3 pyramidal neurons), the synaptic plasticity that occurs (LTP or long term synaptic depression - LTD) varies between individual cells. A variety of sources of calcium including NMDA receptors, metabotropic glutamate receptors, inositide trisphosphate receptors (IPaRs), ryanodine receptors and voltage activated calcium channels all contribute to this process in these neonatal visual cortical neurons. The outcome of LTP or LTD in the neonatal cortex is predicted by the intracellular dendritic calcium transient's kinetic profile that occurs during the individual correlations and the kinetics of the cumulative calcium wave that spreads to the cell body. This protocol offers a unique window into the initial underlying calcium signaling processes that determines polarity of synaptic changes in the visual cortex during postnatal development and provides a new provocative view of how kinetics and amplitude of the very first calcium signals may be critical in the subsequent downstream activation of plasticity. This project also provides the first comprehensive analysis of unitary synaptic connections between individual layer 4 and layer 2/3 neurons with dual patch recording from synaptically coupled pairs with analysis of plasticity and calcium signaling at those connections. We determine the effects of intrinsic cellular differences, maturation, previous experience (metaplasticity) and calcium sources on the signaling and plasticity processes.

描述(由申请人提供)：大脑皮层中的突触在一生中经历其效率的动态变化。特别是，初级视觉皮质的神经元可以利用这种突触可塑性来对视觉处理的各个方面进行并行计算。突触信号的这种依赖活动的变化被认为有助于视觉感知、认知表现、技能学习、发育重组和功能视皮层突触网络的完善以及损伤后的适应性反应。这些形式的可塑性在其健壮性、内在和外在因素的调节以及出生后发育过程中的潜在分子过程中经历了戏剧性的变化。然而，这些形式的功能性突触可塑性的发育调节却较少受到关注。我们利用一个新皮质突触可塑性的实验模型，该模型基于突触输入与突触后神经元激活的一系列相关性，以表征通常导致长期突触增强(LTP)的初始细胞内钙触发事件。有趣的是，在新生儿的视皮层中，当对同一类神经元(第2/3层锥体神经元)应用相同的系列相关时，发生的突触可塑性(LTP或长期突触抑制-LTD)在不同细胞之间有所不同。NMDA受体、代谢性谷氨酸受体、肌醇三磷酸受体(IPaRs)、兰尼定受体和电压激活钙通道等多种钙离子来源都参与了这些新生视皮层神经元的这一过程。LTP或LTD在新生大脑皮层的结果是通过个体相关过程中细胞内树突状钙瞬变的动力学特征和扩散到细胞体的累积钙波的动力学来预测的。这一方案提供了一个独特的窗口来了解最初潜在的钙信号过程，该过程决定了出生后发育期间视觉皮质中突触变化的极性，并提供了一个新的挑衅性观点，即最初的钙信号的动力学和幅度如何在随后的可塑性下游激活中起关键作用。该项目还首次全面分析了单个第4层和第2/3层神经元之间的单一突触联系，并对这些联系的可塑性和钙信号进行了分析。我们确定固有的细胞差异、成熟度、先前的经验(变塑性)和钙来源对信号和可塑性过程的影响。