The functional role of interneuron classes in the mouse visual cortex

描述（由申请人提供）：理解GABA能抑制性中间神经元的作用对于任何脑功能模型都是至关重要的。中间神经元对正常的皮层处理至关重要，它们的功能障碍被认为会产生从精神分裂症到癫痫的一系列疾病。我们的目标是了解不同类别的中间神经元在小鼠视觉皮层2/3层的功能组织中的作用。更好地理解不同类别的中间神经元的功能特性可以允许靶向潜在的治疗性治疗以特异性地改善疾病过程。我们将应用新技术来研究小鼠皮层中几乎每个神经元的生理学，其中标记了不同的中间神经元亚类。通过结合双光子钙成像和转基因小鼠技术，我们将解决以下具体目标：目标1：我们将检查小鼠初级视皮层神经元群体的视觉反应。将测量2/3层体积中数千个神经元的方向选择性、眼优势和视网膜病变。从过去的工作中，我们期望找到良好的方向调谐，但对不同方向做出反应的神经元将混合在一起。这种盐和胡椒的方向排列意味着在局部回路中的神经元之间存在特定的连接。我建议研究这个课题的一个重要方面，抑制性中间神经元在这样一个网络中的作用。目的二：研究小鼠视皮层中间神经元亚类的感受野特性。双光子钙成像将应用于现有的转基因小鼠，其中不同的亚群的interneurons标记。我们假设，一类中间神经元（快速尖峰，小白蛋白阳性细胞）将是强烈的反应，但非选择性的方向。对其他类型的细胞，如低阈值尖峰细胞、生长抑素阳性细胞，我们知之甚少，无法对它们做出具体的预测。但是，某些抑制性中间神经元可能具有很强的刺激选择性。对大量神经元进行采样的能力将有助于表征稀有细胞类型。更一般地说，将全面的局部电路生理学与小鼠遗传学相结合，将加速我们对电路及其组件如何构成功能和行为的理解。

DESCRIPTION (provided by applicant): Understanding of the role of GABAergic inhibitory interneurons is central to any model of brain function. Interneurons are critical to normal cortical processing and their dysfunction is thought to produce an array of disorders ranging from schizophrenia to epilepsy. Our goal is to understand the role of different classes of interneurons in the functional organization of layers 2/3 of the mouse visual cortex. A better understanding of the functional properties of distinct classes of interneurons may allow targeting of potential therapeutic treatments to specifically ameliorate disease processes. We will apply new techniques to study the physiology of virtually every neuron in a volume of cortex in mice in which distinct subclasses of interneurons are labeled. By combining two-photon calcium imaging and transgenic mouse technology we will address the following Specific Aims: Aim1: We will examine the visual responses of neuronal populations in mouse primary visual cortex. Orientation selectivity, ocular dominance and retinotopy will be measured for thousands of neurons in a volume of layer 2/3. From past work, we expect to find good orientation tuning, but neurons that respond to different orientations will be mixed together. The salt-and-pepper arrangement of orientation implies that there are specific connections among neurons in the local circuit. I propose to study one important aspect of this topic, the role of inhibitory interneurons in such a network. Aim 2: We will examine the receptive-field properties of interneuron subclasses in mouse visual cortex. Two-photon calcium imaging will be applied to existing lines of transgenic mice in which distinct subpopulations of interneurons are labeled. We hypothesize that one class of interneurons (fast-spiking, parvalbumin-positive cells) will be strongly responsive, but non-selective for orientation. Too little is known of other classes, such as low-threshold spiking, somatostatin-positive cells, to make specific predictions about them. But, it is likely that some classes of inhibitory interneurons will have strong stimulus selectivity. The ability to sample large populations of neurons will help characterize rare cell types. More generally, combining comprehensive local circuit physiology with mouse genetics will accelerate our understanding how circuits and their components underlie function and behavior.