Circuit mechanisms underlying simple forms of visual memory

动物必须适应不断变化的环境，并了解环境的哪些方面是重要的，哪些是不重要的。为了做到这一点，大脑必须调整视觉信息的处理方式，以抑制对与动物无关的特征的神经反应，同时放大有用的信息，例如指示食物或危险的信息。这种“可塑性”是大脑的一种普遍特性，可以在不同的时间尺度上发生。几秒钟内的变化，比如调整对较暗房间的视觉灵敏度，被称为适应。其他过程可能在几天内发生。例如，当重复的刺激不能提供有用的信息时，习惯化可以抑制神经对它的反应。但是，如果同样的刺激与食物或饮料搭配在一起，习惯化就会受阻，反应反而会增强。这个项目旨在了解快速适应和这些简单形式的长期记忆是如何联系在一起的，以及相同的神经回路是否可以控制两者。我们将通过研究视觉刺激如何在大脑皮层产生神经反应来做到这一点，使用清醒的小鼠和专门的光学显微镜，可以实时观察到大量神经元的电活动，因为每个神经元的光发射变化。大脑可塑性的一个重要的一般机制是改变神经元之间连接的强度。这些神经元可以是兴奋性的，也可以是抑制性的，神经元接收到的兴奋和抑制之间的平衡的变化决定了它的反应是增加还是减少。我们将特别关注不同类型的抑制性神经元如何连接到不同的回路中，这些回路决定了兴奋性神经元的反应。我们最近获得了关于抑制性神经元如何在秒级时间尺度上增加或减少反应的新信息，我们的一般假设是，这些相同回路中的连接要么加强，要么减弱，以建立简单形式的视觉记忆，如习惯化或巴甫洛夫学习。我们将通过观察这些回路的不同组成部分（也就是不同类型的神经元）的活动，以及在每秒钟的基础上人为地增加或减少它们的活动，来测试关于潜在回路的想法。这个项目的信息将帮助我们了解大脑中的神经元如何在不同的时间尺度上调整感觉处理，从而使哺乳动物能够在不断变化的世界中生存。

Animals must navigate a constantly changing environment and learn which aspects of that environment are important and which are not. To allow this, the brain must adjust how visual information is processed to suppress neural responses to features that are of no revelance to the animal while amplifying information that is useful, for instance indicating food or danger. Such "plasticity" is a general property of the brain and can occur on different time-scales. Changes over seconds, such as adjusting visual sensitivity to a darker room, is called adaptation. Other processes can occur over days. Habituation, for instance, can inhibit neural responses to a repeated stimulus when it does not provide useful information. But if the same stimulus is paired with food or drink, habituation is blocked and responses can instead be enhanced. This project aims to understand how fast adaptation and these simple forms of long-term memory are linked and whether the same neural circuits can control both. We will do this by studying how visual stimuli generate neural responses in the cerebral cortex using awake mice and specialized optical microscopes that allow the electrical activity of large numbers of neurons to be observed in real-time as changes in light emission from each neuron. An important general mechanism of plasticity in the brain is to change the strength of the connections between neurons. These neurons can be either excitatory or inhibitory and it is changes in the balance between the excitation and inhibition that a neuron receives that determines whether its response is increased or decreased. Our particular focus will be on how inhibitory neurons of different types are connected into different circuits that determine the responses of the excitatory neurons. We have recently obtained new information about how inhibitory neurons can increase or decrease responses on time-scales of seconds and our general hypothesis is that the connections within these same circuits are either strengthed or weakened to establish simple forms of visual memory such as habituation or Pavlovian learning. We will test ideas about the underlying circuits by observing the activity of different components of these circuits (that is to say different types of neurons) as well as artificially increasing or decreasing their activity on a second-to-second basis. The information from this project will help us understand how neurons in the brain adjust sensory processing on different time-scales to allow a mammal to operate in a changing world.