Synaptic Receptive Field of Auditory Cortical Inhibitory Neuron

实现对听觉皮质功能的理解的一个重要步骤是确定信息如何 包含在感觉输入中的信息在不同的单个皮质神经元中被表达和处理。最近， 几个实验室已经成功地应用了一种在体全细胞电压钳记录技术 大脑皮层神经元。这项技术可以将感觉驱动的兴奋性和抑制性突触输入分解到 记录的神经元，从而可以构建突触连接模型来预测神经元的 在任意感觉刺激下的反应。尽管此技术可以与POST-HOC相结合 组织学方法重建记录细胞的形态，但其“盲性”性质在很大程度上限制了其 有潜力检查皮质中的各种细胞类型，特别是那些体积较小或空间上较小的细胞 稀疏；盲膜片钳记录技术通常会导致锥体细胞的偏向采样 大脑皮层的神经元。 在这个探索性的项目中，我们将研究一种新的技术来揭示功能性突触输入 双光子成像引导的全细胞(TPGWC) 记录其中荧光标记的神经元通过双光子成像被可视化，并特别 用于补丁记录的目标。这项技术在很大程度上得益于鼠标的最新发展 用荧光蛋白标记特定细胞类型的遗传学，如绿色荧光蛋白 (GFP)，其表达受细胞类型特异性启动子控制。最初，我们计划将此应用于 小鼠初级神经元输入层(L3/4)GFP标记GABA能中间神经元的记录技术 听觉皮质(A1)，旨在解决两个基本问题：a)什么是阈值下/峰电位TRF 铝抑制神经元具有哪些特性？B)皮层兴奋性和抑制性突触是如何 输入决定A1抑制神经元的阈值下/棘波TRF结构？

An essential step to achieving an understanding of auditory cortical function is determining how information contained in sensory inputs is represented and processed in different individual cortical neurons. Recently, several laboratories have successfully applied a "blind" in vivo whole-cell voltage-clamp recording technique to cortical neurons. This technique can resolve sensory-driven excitatory and inhibitory synaptic inputs onto the recorded neuron, making it possible to construct a synaptic connectivity model to predict the neuron's response under arbitrary sensory stimulation. Although this technique can be combined with post hoc histological methods to reconstruct the morphology of recorded cells, its "blind" nature largely limits its potential in examining various cell types in the cortex, especially those that are small in size or spatially sparse; the "blind" patch-clamp recording technique will normally result in a biased sampling of pyramidal neurons in the cortex. In this exploratory project, we will study a new technique for revealing functional synaptic inputs made onto different types of individual cortical neurons ¿ two-photon imaging guided whole-cell (TPGWC) recording ¿ in which fluorescence-labeled neurons are visualized by two-photon imaging and specifically targeted for patch recording. This technique has largely benefited from recent developments in mouse genetics in the labeling of specific cell types with fluorescence proteins, such as green fluorescence protein (GFP), whose expression is controlled by cell-type specific promoters. Initially, we plan to apply this recording technique to GFP-labeled GABAergic interneurons in the input layers (L3/4) of the mouse primary auditory cortex (A1), and aim at addressing two fundamental questions: a) What subthreshold/spike TRF properties are possessed by Al inhibitory neurons? b) How do cortical excitatory and inhibitory synaptic inputs determine subthreshold/spike TRF structure of A1 inhibitory neurons?