The role of patterned activity in neuronal codes for behavior

 描述(申请人提供)：大脑功能的一个关键方面是神经元群体的活动如何编码用于指导行为的信息。一个长期存在的理解群体编码的模型系统是视觉大脑皮层，因为它的结构和解剖学被很好地理解，而且视觉刺激可以呈现给具有高水平时间和空间控制的受试者。数以千计或更多的神经元对单一的视觉刺激产生动作电位，一个重要的悬而未决的问题是，这种群体反应是如何携带信息的--如何解码这些神经元之间这些峰的详细时间和模式以指导行为。因为众所周知，遗传学控制神经元的身份和形态，并影响它们与哪些其他神经元形成突触伙伴，因此，关于群体中哪些神经元放电尖峰的准确细节似乎对行为至关重要。但令人惊讶的是，过去的实验工作暗示，支配神经元编码的主要数量是一个群体的尖峰总数或平均放电率，这使得这些尖峰的准确时间和空间分布变得不那么重要。理论研究表明，皮层可以支持这两种类型的代码，而且使用的代码类型甚至可能因行为任务的不同而不同。然而，由于无法以图案化的方式改变神经元的活动，因此还不可能明确地确定皮质种群代码是如何用于行为的。在这个项目中，我们将 使用双光子个体发生刺激来激活行为动物的神经元模式，以了解种群代码如何控制行为的细节。这项工作是通过结合光学波前整形方法来控制双光子光学焦点体积的大小和形状，以及在老鼠身上使用心理物理行为方法来精确量化动物在神经元模式受到刺激时的感知表现而实现的。我们将使用双光子模式刺激来重播自然发生的种群反应，以确定它们是否对动物具有特殊意义，可能是因为这些模式是由基本的突触连接决定的。通过使用模式刺激来改变神经元之间的活动相关性，我们还将测试之前观察到的两个神经元的放电活动之间的关系是否是神经元代码的重要组成部分。为了实现我们的目标，我们将生产一种新技术，用于刺激具有单细胞特异性的行为动物大脑中的神经元，该技术可以适用于在广泛的动物模型和行为中探索神经元动力学。

 DESCRIPTION (provided by applicant): A key aspect of brain function is how the activity of neuronal populations encodes information that is used to guide behavior. A longstanding model system to understand population coding is the visual cerebral cortex, because its structure and anatomy are well understood, and because visual stimuli can be presented to subjects with high levels of temporal and spatial control. Thousands or more neurons fire action potentials in response to a single visual stimulus, and an important open question is how this population response carries information - how the detailed timing and pattern of these spikes across neurons is decoded to guide behavior. Because it is known that genetics controls the identity and morphology of neurons, and influences which other neurons they form synaptic partners with, it appears likely that the precise details of which neurons in a population fire spikes is vitally important for behavior. But surprisingly, past experimental work hints that the primary quantity governing neuronal coding is the total number of spikes or average firing rate across a population, making the precise timing and spatial distribution of those spikes less important. Theoretical work shows that either type of code can be supported by the cortex and that the type of code used may even vary from one behavioral task to the next. However, it has not been possible to definitively determine how cortical population codes are used for behavior because of the inability to change the activity of neurons in a patterned fashion. In this project, we will use two-photon ontogenetic stimulation to activate patterns of neurons in behaving animals to understand the details of how population codes control behavior. This work is made possible by the combination of optical wave front-shaping methods to control the size and shape of a two- photon optical focal volume, and psychophysical behavioral methods in mice that allow precise quantification of animals' perceptual performance when neuronal patterns are stimulated. We will use two-photon patterned stimulation to replay naturally-occurring population responses to determine if they have special meaning to the animal, perhaps because those patterns are determined by essential synaptic connections. By using patterned stimulation to vary the activity correlation between neurons, we will also test whether previously-observed pairwise correlations, which measure the relationship between the firing activities of two neurons, are an important part of the neuronal code. In achieving our goals we will produce a new technology for stimulating neurons in the brains of behaving animals with single-cell specificity that can be adapted to explore neuronal dynamics in a wide range of animal models and behaviors.