Precise mapping of functional somatotopy in sensorimotor cortex

最近在活体动物成像方面的创新使得能够实时测量完整大脑中的细胞信号，并可视化形成大脑功能框架的神经元的微观结构。通过将这些细胞成像技术与局部功能成像和脑解剖学测量相结合，这项研究将精确地绘制出小鼠和大鼠大脑皮质与肢体感觉相关的功能、连通性和适应性变化。区域成像绘制了对感觉刺激作出反应的大脑皮层区域，而感觉诱发的钙信号的细胞成像能够同时评估尖峰活动和数百至数千个光学记录的神经元的精确三维组织。这些成像技术利用刺激将精确的机械刺激传递到前爪或后爪的离散区域，从而精确地绘制出对肢体不同区域的刺激做出反应的皮质区域之间的边界。此外，钙指示剂的给药方式允许对单个轴突和突触进行亚细胞分辨率的钙成像。因此，我们的成像方法可以定义精确的三维功能组织，这是任何其他方法都不可能实现的。还将在这些功能图中进行有针对性的神经元示踪剂注射，这种化合物使人们能够识别投射到注射部位或从注射部位接收投射的单个神经元，以便可以描述这些离散的体感区域的投射的组织。最后，为了评估行为经验如何改变功能表征的形状、单个神经元的活动及其解剖联系，上述成像和轨迹跟踪技术将在接受环境丰富、自愿耐力训练或达到技能训练的大鼠身上进行。综合考虑，这些研究将创新的成像技术与既定的神经束追踪方案相结合，以确定啮齿动物感觉运动皮质的神经元组织和经验相关的可塑性。

Recent innovations in live animal imaging permit real-time measurement of cellular signalling in the intact brain and visualization of the microscopic structure of the neurons that form the framework for brain function. By combining these cellular imaging techniques with regional functional imaging and measures of brain anatomy, this research will precisely map the function, connectivity, and adaptive changes the cortex associated with limb sensation in mice and rats. Regional imaging maps the cortical areas responsive to sensory stimulation, while cellular imaging of sensory-evoked calcium signals enables simultaneous assessment of spiking activity and the precise three-dimensional organization of hundreds to thousands of optically-recorded neurons. Using stimuli that deliver precise mechanical stimulation to discrete regions of the fore- or hind-paw, these imaging techniques will precisely map the borders between regions of cortex responding to stimulation of different areas of the limbs. Moreover, calcium indicators can be administered in a manner that permits calcium imaging with subcellular resolution to single axons and synapses. As such, our imaging approach can define precise three-dimensional functional organization not possible through any other method. Targeted injections of neuronal tracers, compounds that allow one to identify the individual neurons that project to or receive projections from the injection site, will also be made within these functional maps such that the organization of the projections to and from these discrete somatosensory regions can be described. Finally, to assess how the shape of the functional representations, the activity of individual neurons, and their anatomical connections are altered by behavioural experience, the imaging and tract tracing techniques described above will be performed in rats undergoing environmental enrichment, voluntary endurance exercise, or skilled-reaching training. Combined, the proposed studies combine innovative imaging techniques with established protocols for neuronal tract tracing to define the neuronal organization and experience-dependent plasticity of the rodent sensorimotor cortex.