Neural pathways and behavioral state in the mouse visual system

描述（由申请人提供）：我们的研究目的是了解视觉加工如何受到行为需求的影响。视丘脑（膝状背外侧核，LGN）在这一过程中起着关键作用，因为它在视网膜和皮层之间提供了一个中间中继，其中传输可以根据多个调节输入进行动态调节。尽管在体外和麻醉下对丘脑功能进行了广泛的研究，但我们仍然不了解清醒视觉处理过程中行为状态如何调节LGN的多条通路。为了解决这个问题，我们将研究老鼠的视觉系统，以便利用现有的分子遗传工具来识别和操纵潜在的神经回路。在我们的第一个目标中，我们将描述小鼠LGN中存在的视觉通路，包括神经编码和空间组织，通过高密度体内电生理测量。接下来，我们将通过测量警觉受试者与运动相关的视觉诱发神经活动的变化，确定这些通路中的信息是如何被行为状态调节的。最后，我们将测试神经调节输入在调节行为状态影响中的作用，使用胆碱能电路的光遗传学操作。这项工作将促进我们对大脑中信息的选择性门控的理解，这对视觉功能和认知过程都是必不可少的。

DESCRIPTION (provided by applicant): The goal of our research is to understand how visual processing is influenced by behavioral demands. The visual thalamus (dorsal lateral geniculate nucleus, LGN) plays a key role in this process, as it provides an intermediate relay between the retina and cortex, where transmission can be dynamically regulated based on multiple modulatory inputs. Although thalamic function has been studied extensively in vitro and under anesthesia, we still do not understand how behavioral state modulates the multiple pathways in LGN during awake visual processing. To address this gap we will study the mouse visual system, in order to take advantage of the range of molecular genetic tools that are available to identify and manipulate the underlying neural circuits. In our first aim, we will delineate the visal pathways present in mouse LGN, both in terms of neural coding and spatial organization, as measured with high-density in vivo electrophysiology. Next, we will determine how information in these pathways is modulated by behavioral state, by measuring the changes in visually-evoked neural activity associated with locomotion in alert subjects. Finally, we will test the role of neuromodulatory inputs in mediating the effects of behavioral state, using optogenetic manipulation of cholinergic circuitry. This work will advance our understanding of the selective gating of information in the brain, which is essential for both visual function and cognitive processes.