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.

摘要 在出生后的发展过程中，感觉系统通过经验变得适应，从 复杂的自然环境。在这段敏感期内暂时剥夺视觉输入 破坏视觉功能一旦成熟，这些回路就稳定下来，不需要持续的视觉输入， 保持功能。传统上，视力的发展和拯救是使用简单的定向光条来研究的 由不同的空间频率（光栅刺激）组成。虽然光栅刺激有效地驱动大多数 初级皮质（V1）神经元的刺激，是用于定义发育里程碑的刺激， 在双眼之间的双眼对准中，众所周知，简单的光栅刺激不是优选的 刺激大多数神经元在成人V1，在一系列物种。此外，对复杂特征的选择性 不能用简单刺激引起的反应特征来解释;这可能是多个刺激的一般原理。 感觉形态目前尚不清楚对复杂特征的反应何时成熟，也不清楚是否成熟。 改善光栅空间敏锐度的干预拯救了弱视小鼠的双眼视觉或复杂反应。 为了填补这一知识空白，我们将定义复杂反应的发展轨迹， 建立里程碑，并确定条件，促进救援复杂功能的处理，在视觉上 被剥夺的老鼠将使用双光子钙成像纵向监测双眼V1的神经活动 在对照和剥夺小鼠中，结合细胞类型特异性操作。对光栅和 将在单神经元和群体水平上评估复杂刺激。我们最近证明， 视觉体验推动了对复杂性偏好的转变;这种成熟的时间发生在高峰之后 关键时期。基于这些结果，在目标1中，我们将检验复杂特征反应 在经典定义的关键期之后，对视觉剥夺和复杂特征处理仍然敏感 随着动物扩大视觉引导的行为库而继续发展。越来越多的证据 表明生长抑素（SOM）协同血管活性肠肽（VIP）抑制中间神经元 介导上下文环绕调制，这是处理复杂场景的基本属性。 因此，在目标2中，我们将描述SOM响应的成熟和光栅的稳定性。 相对于复杂特征响应的出现的响应调谐。最后，在目标3中，我们将测试 假设丰富的经验，在联想训练的形式，加速稳定的双眼 在弱视小鼠中，当通过恢复黑暗进行时， exposure.这些目标的成功完成将提供关键的细胞类型的具体细节， 对复杂特征的反应来自一个网络，该网络由天生适应简单光栅的神经元组成 刺激在健康和弱视小鼠。