Transgenic Dissection of the Neural Circuitry of the Intact Hippocampal Formation

描述(申请人提供)：本申请描述了分析海马体结构(HF)神经回路的实验，海马体结构是与记忆以及阿尔茨海默氏症和相关痴呆症等障碍最明显相关的大脑区域。它将神经元特异性转基因表达与电生理技术相结合，在细胞和网络水平上研究哺乳动物海马结构中的信息转换。这种方法类似于工程师用来分析电子电路的节点分析方法。然而，这里的节点是神经细胞类型，而不是电子组件。这些节点是由转基因“驱动”系指定的，这些“驱动”系指导各种转基因(取决于它们与哪些转基因“有效载荷”系交叉)的表达，从而使细胞类型特定的活性发生变化。在执行节点分析时，我们在处理一个节点的活动时同时记录其他节点的活动，就像控制放大器电路的阻抗的电位器在操作时改变音频输出一样。我们通过驱动转基因的表达来做到这一点，转基因在被特定的药物或波长的光激活时，会增加或降低神经细胞的膜电位。然后，我们可以操纵高频回路中可识别的初级神经元群体的活动，同时记录其他神经元的活动，从而获得信息如何从一个区域转换到下一个区域的功能性理解。

DESCRIPTION (provided by applicant): This application describes experiments that analyze the neural circuitry of the hippocampal formation (HF), the brain area most clearly implicated in memory and disorders such as Alzheimer's and related dementias. It combines neuron-specific transgene expression with electrophysiological techniques to study the transformation of information in the mammalian hippocampal formation at the cellular and network level. The approach is similar to the nodal analysis performed by engineers to analyze electronic circuits. Here, however, the nodes are neural cell types rather than electrical components. The nodes are specified by transgenic "driver" lines which direct the expression of various transgenes (depending upon which transgenic "payload" lines they are crossed to) enabling cell type specific changes in activity. Performing this nodal analysis, we manipulate the activity of one node while recording from others, much as when a potentiometer controlling the impedance of an amplifier circuit changes audio output when manipulated. We do so by driving the expression of transgenes which increase or decrease the membrane potential of neurons when activated either by specific drugs or wavelengths of light. We can then manipulate the activity of an identifiable population of primary neurons in the HF circuit while recording the activity of others gaining a functional understanding of how information is transformed from one region to the next.