Development of Synaptic Plasticity in Visual Cortex

描述（由申请人提供）：大脑皮层中的突触在整个生命过程中经历其效率的动态变化。特别是，初级视觉皮层的神经元可以使用这种突触可塑性来执行视觉处理方面的并行计算。这种活动依赖性的变化，突触信号已被认为有助于视觉感知，认知能力，技能学习，发育重组和完善功能性视觉皮层突触网络和损伤后的适应性反应。这些形式的可塑性经历了巨大的变化，其鲁棒性，调制的内在和外在因素和潜在的分子过程在出生后的发展。然而，这些形式的功能性突触可塑性的发育调控受到较少的关注。我们利用新皮层突触可塑性的实验模型，该模型是基于突触输入与突触后神经元激活的串行相关性来表征通常导致长时程突触增强（LTP）的初始细胞内钙触发事件。有趣的是，在新生儿视觉皮层中，当相同的序列相关性应用于相同类别的神经元（2/3层锥体神经元）时，发生的突触可塑性（LTP或长期突触抑制- LTD）在个体细胞之间变化。多种钙源包括NMDA受体、代谢型谷氨酸受体、三磷酸肌醇受体（IPaR）、兰尼碱受体和电压激活的钙通道都有助于这些新生视皮层神经元中的这一过程。LTP或LTD在新生儿皮层的结果是预测的细胞内树突状细胞钙瞬变的动力学曲线，发生在个人的相关性和动力学的累积钙波传播到细胞体。该协议提供了一个独特的窗口到最初的潜在钙信号传导过程，决定极性的突触变化在视觉皮层在出生后的发展，并提供了一个新的挑衅性的观点，如何动力学和振幅的第一个钙信号可能是至关重要的，在随后的下游激活可塑性。该项目还提供了第一次全面分析单个第4层和第2/3层神经元之间的单一突触连接，并从突触耦合对中记录双贴片，分析这些连接处的可塑性和钙信号。我们确定内在的细胞差异，成熟，以前的经验（metaplasticity）和钙源的信号和可塑性过程的影响。

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.