Mechanisms and plasticity of history-dependent processing in the visual cortex

摘要 适应是感觉处理的基本特征，最近的感觉体验 形状对当前输入的响应。这种现象在不同物种中都有观察到， 系统，和处理阶段，并已被证明参与机制，引起跨 从毫秒到小时的时间尺度范围。在视觉系统中，眼睛和头部的快速运动 使适应的时间尺度更短，特别是与确定感觉编码有关， 持续的行为我们最近发现了一种在清醒状态下的快速的、特定于刺激的适应形式 小鼠初级视觉皮层（V1），其参与的时间为毫秒，持续时间为秒。 重要的是，在这个时间尺度上的适应对于感觉处理是重要的，因为它极大地损害了 方向辨别任务的表现。因此，我们的目标是确定 这是幅度、时程和刺激特异性适应的基础，目的是确定 适应如何在视觉层次和行为状态中塑造感官处理。在 特别是，我们将测试的假设，适应在很大程度上是由皮质-皮质短期 突触抑制，并在行为环境的特定控制下。在目标1中，我们将使用内部- 和细胞外记录结合光学和化学遗传学操作，以确定 皮质-皮质突触的抑制对适应的贡献。我们还将测试 其他机制包括激活内在电导，募集抑制性 机制，以及兴奋和抑制平衡的变化。在目标2中，我们将使用细胞外 记录来测量兴奋性和兴奋性神经元适应的幅度、时程和特异性， V1和高级视觉区的抑制性神经元。这将揭示适应是如何沿着沿着 视觉皮层层次，特别关注腹侧流，这被认为是支持 通过自适应进行物体识别。在目标3中，我们将研究行为背景对 适应我们的初步数据表明，适应的特异性在幼稚小鼠中是不同的， 这些小鼠执行方向辨别任务。我们将确定具体的行为 情境（任务参与与培训）控制适应，并调查电路 支持这种可塑性的机制。总之，这些实验将揭示如何快速适应 塑造并潜在地丰富了视觉区域和行为环境中的感觉处理。我们 我希望这些结果能够揭示跨感觉区域适应的一般原则， 以及专门支持视觉处理和感知的机制。

Abstract Adaptation is a fundamental feature of sensory processing whereby recent sensory experience shapes responses to current input. This phenomenon has been observed across species, sensory systems, and stages of processing and has been shown to engage mechanisms that are induced across a range of time-scales from milliseconds to hours. In the visual system, rapid eye and head movements make shorter time-scales of adaptation particularly relevant for determining sensory encoding during ongoing behavior. We have recently identified a form of rapid, stimulus-specific adaptation in the awake mouse primary visual cortex (V1) that is engaged on the scale of milliseconds and persists for seconds. Importantly, adaptation on this time-scale is important for sensory processing as it dramatically impairs performance on an orientation discrimination task. Thus, our goal here is to determine the mechanisms that underlie the magnitude, time-course and stimulus specificity adaptation with the aim of determining how adaptation shapes sensory processing across the visual hierarchy and behavioral states. In particular, we will test the hypothesis that adaptation is largely determined by cortico-cortical short-term synaptic depression and is under the specific control of behavioral context. In Aim 1, we will use intra- and extracellular recordings in combination with opto- and chemogenetic manipulations to determine the contribution of depression at cortico-cortical synapses to adaptation. We will also test the contribution of other mechanisms including activation of intrinsic conductances, recruitment of suppressive mechanisms, and changes in the balance of excitation and inhibition. In Aim 2, we will use extracellular recordings to measure the magnitude, time-course and specificity of adaptation in excitatory and inhibitory neurons in V1 and the higher visual areas. This will reveal how adaptation accumulates along the visual cortical hierarchy, with a particular focus on the ventral stream which is thought to support object recognition through adaptation. In Aim 3, we will investigate the impact of behavioral context on adaptation. Our preliminary data reveal that the specificity of adaptation is different in naïve mice and those mice performing an orientation discrimination task. We will determine the specific behavioral contexts (task engagement versus training) that control adaptation, and investigate the circuit mechanisms that support this plasticity. Together, these experiments will reveal how rapid adaptation shapes, and potentially enriches, sensory processing across visual areas and behavioral contexts. We expect that these results will reveal general principles underlying adaptation across sensory areas, as well as mechanisms that are specialized to support visual processing and perception.