Development and plasticity of stimulus processing in the visual cortex

摘要 在出生后的发育过程中，感觉系统通过经验适应，从 复杂的自然环境。在这一敏感期内视觉输入的暂时性剥夺 会破坏视觉功能。一旦成熟，这些电路就会稳定下来，不需要连续的视觉输入来 保持功能。传统上，视觉的发展和拯救是用简单的定向光条来研究的 由不同的空间频率(栅格刺激)组成。尽管格栅刺激有效地驱动了大多数 是用来定义发育里程碑的刺激，例如 双眼之间的双眼对齐，这是众所周知的，简单的光栅刺激并不是首选 刺激成年V1中的大多数神经元，跨越一系列物种。此外，对复杂特征的选择性 不能用简单刺激引起的反应PROfiLES来解释；这可能是多个 感官模式。目前尚不清楚对复杂功能的响应何时成熟，也不知道是否 改善格栅空间敏锐度的干预措施挽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，并确定促进视觉上复杂要素处理的条件 剥夺了小鼠的权利。双眼V1的神经活动将使用双光子钙成像进行纵向监测 在对照组和剥夺小鼠中，结合细胞类型的特异性操作。对格栅的响应和 复杂刺激将在单个神经元和群体水平上进行评估。我们最近证明了 视觉体验推动了对复杂性的偏好转变；这种成熟的时机发生在高峰之后 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的假设 在经典定义的关键期和复杂特征处理后，保持对视觉剥夺的敏感性 随着动物扩大其视觉引导的行为能力，这种能力继续发展。积累证据 提示生长抑素(SOM)与血管活性肠肽(VIP)抑制中间神经元协同作用 协调上下文环绕调制，这是处理复杂场景的基本属性。 因此，在目标2中，我们将表征SOM响应的成熟度和光栅的稳定性。 与复杂特征反应的出现相关的反应调整。最后，在目标3中，我们将测试 以联想训练的形式丰富经验加速双眼稳定的假说 弱视小鼠在恢复暗视时的排列和改善复杂特征的处理 曝光。成功完成这些目标将提供关键的细胞类型具体细节，如 对复杂特征的反应来自一个由神经元组成的网络，这些神经元天生就被调谐到简单的栅格上 对健康和弱视小鼠的刺激。

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.