Development and plasticity of stimulus processing in the visual cortex

视觉皮层刺激处理的发展和可塑性

• 批准号: 10572887
• 负责人: SANDRA J KUHLMAN
• 金额: $ 51.12万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10572887
• 关键词: Acceleration; Adolescent; Adult; Age; Age Months; Amblyopia; Animals; Behavioral; Binocular Vision; Calcium; Code; Complex; Darkness; Data; Development; Environment; Eye; Felis catus; Frequencies; Goals; Image; Interneurons; Intervention; Knowledge; Light; Location; Maintenance; Mediating; Methods; Modality; Modeling; Monitor; Monkeys; Mus; Neurons; Ocular Dominance; Population; Property; Recovery; Rejuvenation; Rodent; Sensory; Somatostatin; Stimulus; Structure; Testing; Time; Training; Vasoactive Intestinal Peptide; Vision; Vision Disorders; Visual; Visual Cortex; Work; cell type; critical period; excitatory neuron; experience; improved; monocular deprivation; neural; postnatal development; preference; preservation; receptive field; response; sensory system; stimulus processing; two-photon; visual deprivation; young adult

Abstract During postnatal development sensory systems become adapted, through experience, to extract features from complex natural environments. Transient deprivation of visual input during this sensitive period permanently disrupts visual function. Once mature, these circuits are stabilized and do not require continuous visual input to maintain function. Traditionally, development and rescue of vision is studied using simple oriented bars of light composed of varying spatial frequencies (grating stimuli). Although grating stimuli effectively drive the majority of neurons in the primary cortex (V1) and are the stimuli used to define developmental milestones such as binocular alignment between the two eyes, it is well-recognized that simple grating stimuli are not the preferred stimuli for most neurons in adult V1, across a range of species. Furthermore, selectivity to complex features cannot be explained by response profiles evoked by simple stimuli; this is likely a general principle for multiple sensory modalities. It is unknown when responses to complex features become mature, nor whether interventions that improve grating spatial acuity rescue binocular vision or complex responses in amblyopic mice. To fill this gap in knowledge we will define the developmental trajectory of complex responses relative to established milestones, and identify conditions that facilitate the rescue of complex-feature processing in visually deprived mice. Neural activity in binocular V1 will be longitudinally monitored using 2-photon calcium imaging in control and deprived mice, in combination with cell-type specific manipulation. Responses to grating and complex stimuli will be assessed at the single-neuron and population levels. We recently demonstrated that visual experience drives a shift in preference for complexity; the timing of this maturation occurs after the peak of the critical period. Based on these results, in Aim 1 we will test the hypothesis that complex-feature responses remain sensitive to visual deprivation past the classically defined critical period, and complex-feature processing continues to develop as animals expand their visually-guided behavioral repertoire. Accumulating evidence indicates that somatostatin (SOM) in coordination with vasoactive intestinal peptide (VIP) inhibitory interneurons mediate contextual surround modulation, a property that is fundamental to processing complex scenes. Therefore, in Aim 2 we will characterize the maturation of SOM responses and the stabilization of grating- response tuning relative to the emergence of complex-feature responses. Finally, in Aim 3 we will test the hypothesis that enriched experience, in the form of association training, accelerates the stabilization of binocular alignment and improves complex-feature processing in amblyopic mice when proceeded by rejuvenating dark exposure. Successful completion of these aims will provide crucial cell-type specific details regarding how responses to complex features emerge from a network comprised of neurons innately tuned to simple grating stimuli in healthy and amblyopic mice.

抽象的 在产后发展期间，通过经验来调整感官系统，从 复杂的自然环境。在这个敏感时期内，视觉输入的瞬时剥夺永久性 破坏视觉功能。一旦成熟，这些电路就会稳定，不需要连续的视觉输入 保持功能。传统上，使用简单的光线杆研究了视觉的发展和拯救 尽管刺激有效地推动了大多数 原发性皮质（V1）中的神经元的刺激是用于定义发展里程碑的刺激 两只眼睛之间的双眼对准，众所周知，简单的光栅刺激不是首选 大多数成人V1中大多数神经元的刺激，遍布各种物种。此外，对复杂特征的选择性 不能用简单刺激引起的响应纤维来解释；这可能是多重的一般原则 感官方式。当对复杂特征的响应变得成熟时，尚不清楚 改善光泽空间敏锐度拯救双眼视觉或弱视小鼠复杂反应的干预措施。 为了填补这一空白，我们知道我们将定义相对于复杂响应的发展轨迹 已建立的里程碑，并确定有助于在视觉上挽救复杂功能处理的条件 被剥夺的老鼠。双眼V1中的神经活性将使用2光子钙成像纵向监测 在对照和被剥夺的小鼠中，结合细胞类型的特异性操纵。对光栅和 复杂的刺激将在单神经元和人口水平上进行评估。我们最近证明了 视觉体验推动了对复杂性偏爱的转变；这种成熟的时机发生在峰值之后 关键时期。基于这些结果，在AIM 1中，我们将测试复杂功能响应的假设 对经典定义的关键时期和复杂功能处理的视觉剥夺保持敏感 随着动物扩大视觉引导的行为曲目，继续发展。积累证据 表明与血管活性肠肽（VIP）抑制性神经元协调的生长抑素（SOM） 调解上下文周围的调制，这是一种对处理复杂场景至关重要的属性。 因此，在AIM 2中，我们将表征SOM反应的成熟和光栅的稳定 相对于复杂功能响应的出现，响应调整。最后，在AIM 3中，我们将测试 以关联训练的形式丰富经验的假设加速了双眼的稳定 通过使黑暗恢复活力时，对齐并改善了弱视小鼠的复杂功能处理 接触。这些目标的成功完成将为有关如何如何提供有关细胞类型的特定细节 对复杂功能的响应来自于始终调整为简单光栅的神经元的网络中出现的 健康和弱视小鼠的刺激。