Circuit mechanisms governing the development of direction selectivity

描述（由申请人提供）：初级视觉皮层的神经元表现出对各种刺激特征有选择性的反应特性，如方向偏好、眼优势和方向选择性。这些反应特性通常排列在视觉皮层有序的柱状图中，它们的发展受到视觉经验操纵的高度影响。最近的研究结果表明，方向选择性的发展可能是独特的，因为它在眼睛睁开后的头两周内对视觉经验的早期需求。此外，在视觉迟钝的雪貂中，短暂暴露于漂移光栅刺激（运动训练）足以在几小时内驱动方向选择性的出现。本提案中的实验旨在确定皮层回路的哪些元素有助于这种快速出现的方向选择性。来自视网膜的视觉信息通过LGN投射到第4层到达皮层，第4层又投射到第2/3层，在第2/3层，运动训练的效果已经被研究过。该实验将首先通过体内双光子钙成像检查运动训练的眼间转移来区分训练诱导的下丘-皮质突触变化和皮质内机制。随后的实验将探索皮层内部和皮层之间的相互作用，这些相互作用驱动了方向选择性的出现。这些实验将使用第4层的细胞外记录和第2/3层的钙成像来比较每层的初始选择性和运动训练的效果。最后一组实验将使用光遗传学工具在运动训练期间操纵2/3层神经元的神经活动。这些实验将测试训练过程中2/3层视觉驱动活动的存在和模式是否对方向选择性的出现至关重要。综上所述，这些实验将为视觉系统发展的早期事件提供新的见解，这些事件对方向感知的适当成熟至关重要。了解运动刺激的经验如何改变视觉回路，从而产生方向选择性，对于理解视觉感知的这一关键特征，以及更广泛地理解感觉系统的经验依赖发展至关重要。

DESCRIPTION (provided by applicant): Neurons in the primary visual cortex exhibit response properties that are selective for various stimulus features, such as orientation preference, ocular dominance, and direction selectivity. These response properties are commonly arrayed in orderly columnar maps across the visual cortex, and their development is highly affected by manipulations of visual experience. Recent results have suggested that the development of direction selectivity may be unique in its early requirement for visual experience within the first two weeks following eye opening. Furthermore, in visually naove ferrets brief exposure to a drifting grating stimulus (motion training) is sufficient to drive the emergence of direction selectivity in a matter of hours. The experiments in this proposal are designed to determine which elements of the cortical circuit contribute to this rapid emergence of direction selectivity. Visual information from the retina reaches the cortex by way of LGN projections to layer 4, which in turn projects to layer 2/3, where the effects of motion training have been previously studied. The proposed experiments will first distinguish training-induced changes in geniculo- cortical synapses from intracortical mechanisms by examining the interocular transfer of motion training using in vivo two-photon calcium imaging. Subsequent experiments will probe the interactions within and between cortical layers that drive the emergence of direction selectivity. These experiments will use extracellular recordings in layer 4 and calcium imaging in layer 2/3 to compare the initial selectivity in each layer and the effects of motion training. A final set of experiments will use optogenetic tools to manipulate neural activity in layer 2/3 neurons during motion training. These experiments will test whether the presence and pattern of visually driven activity in layer 2/3 during training is essential for the emergence of direction selectivity. Taken together, these experiments will provide novel insights into the early events in visual system development that are critical for the proper maturation of direction perception. Understanding how experience with moving stimuli alters visual circuits to give rise to direction selectivity is crucial to understanding both this key feature of visual perception, and more broadly, the experience-dependent development of sensory systems. PUBLIC HEALTH RELEVANCE: The proper maturation of direction perception is a critical feature of the visual system, and selective deficits in motion perception are prevalent in multiple human developmental disorders, including autism. The proposed research will address how experience with moving stimuli alters visual circuits to give rise to direction selectivity, increasing both the understanding of these disorders and visual development in general.