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

摘要 适应是感觉加工的一个基本特征，最近的感觉经验 形成对当前输入的响应。这种现象已经在物种、感官上观察到了 系统和处理阶段，并已被证明参与了在 时间范围从毫秒到小时不等。在视觉系统中，眼睛和头部的快速运动 使较短的适应时间尺度尤其与确定感觉编码有关 持续的行为。我们最近在清醒状态下发现了一种快速的、特定于刺激的适应 小鼠初级视觉皮质(V1)，以毫秒为尺度参与并持续数秒。 重要的是，在这种时间尺度上的适应对感觉处理很重要，因为它极大地损害了 在方位辨别任务中的表现。因此，我们在这里的目标是确定机制 这是大小、时间进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觉处理。在……里面 特别是，我们将检验这一假设，即适应在很大程度上取决于大脑皮层的短期 突触抑制，处于行为语境的特定控制之下。在目标1中，我们将使用Intra- 以及细胞外记录与光和化学操作相结合来确定 皮质-皮质突触的抑郁对适应的贡献。我们还将测试以下方面的贡献 其他机制包括激活内在电导，招募抑制 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 记录以测量兴奋性和非兴奋性适应的大小、时间进程和特异性 V1区和高级视区的抑制性神经元。这将揭示适应是如何积累起来的。 视觉皮质层级，特别关注腹侧流，它被认为支持 通过自适应进行对象识别。在目标3中，我们将调查行为背景对 适应。我们的初步数据显示，在幼稚的小鼠和 那些执行方位辨别任务的老鼠。我们将确定具体的行为 控制适应的环境(任务投入与培训)，并调查回路 支持这种可塑性的机制。总而言之，这些实验将揭示出适应的速度 形成并潜在地丰富了视觉区域和行为背景中的感觉处理。我们 预计这些结果将揭示跨感觉区域适应的一般原则，如 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.