Circuit and Synaptic Mechanisms of Visual Spatial Attention

感觉处理是一种理解神经回路及其在行为过程中的功能的方法。 行为背景强烈影响感觉加工。例如，一个简短的视觉刺激是 更容易检测到它是否出现在可预测的空间位置。对视觉空间的强烈关注 增强这些部位对刺激的神经和行为反应，但详细的神经 产生这些效应的机制仍不清楚。这很大程度上是因为我们缺乏 能够实时测量特定的神经元、电路和突触 引起视觉空间注意。我们在弥合这一关键的知识鸿沟方面处于独特的地位 具有细胞类型特定光遗传学、多位点硅电极的创新组合 小鼠初级视皮层(V1)的记录和全细胞膜片钳记录 明确的视觉空间注意行为。这种创新的技术组合将 使我们能够1)确定定义的兴奋性和抑制性的响应(增益)调制 空间注意过程中的神经元；2)确定跨皮层的增益调制 空间注意；3)确定空间注意过程中获得调制的突触机制 意义重大。该项目将满足了解内部 认知状态--注意力--在突触、细胞、网络和 行为水平。为注意力和感觉处理建立生物物理基础将 加深对以注意力缺陷为特征的神经性疾病的了解 和感官知觉，如精神分裂症和自闭症。 创新。这项工作通过将多个规模的 在受控良好的感觉行为中来自特定神经回路的测量 空间注意力。我们将结合高密度局域场势和动作势 群体水平的测量，皮层和丘脑的膜片钳测量 突触水平的电路，以及细胞类型特有的光遗传学。我们提供概念性的 通过定义内部认知因素(如注意力)如何调节感觉信号来实现创新 在网络和突触级别的定义电路中。

Sensory processing is a way to understand neural circuits and their functions during behavior. Behavioral context strongly affects sensory processing. For example, a brief visual stimulus is easier to detect if it appears in a predictable spatial location. Attention to visual space strongly enhances neural and behavioral responses to stimuli in those locations, but the detailed neural mechanisms producing these effects remain unknown. This is largely because we lack the ability to measure specific neurons, circuits, and synapses in real-time during behavior that elicits visual spatial attention. We are uniquely positioned to bridge this critical knowledge gap with an innovative combination of cell-type specific optogenetics, multi-site silicon electrode recordings, and whole-cell patch-clamp recordings in mouse primary visual cortex (V1) during a well-defined visual spatial attention behavior. This innovative combination of techniques will enable us to 1) determine response (gain) modulation in defined excitatory and inhibitory neurons during spatial attention; 2) determine gain modulation across cortical layers during spatial attention; 3) determine synaptic mechanisms of gain modulation during spatial attention SIGNIFICANCE. This project will meet a significant need to understand how an internal cognitive state—attention—exerts its effects across synaptic, cellular, network, and behavioral levels. Establishing a biophysical basis for attention and sensory processing will provide greater understanding of neurological disorders characterized by deficits of attention and sensory perception, such as schizophrenia and autism. INNOVATION. This work provides technical innovation by combining multiple scales of measurement from specific neural circuits during a well-controlled sensory behavior that elicits spatial attention. We will combine high-density local field potential and action potential measurements at population level, patch-clamp measurements from cortical and thalamic circuits at the synaptic level, and cell-type specific optogenetics. We provide conceptual innovation by defining how an internal cognitive factor like attention modulates sensory signals in defined circuits across network and synaptic levels.