Neural circuitry underlying non-sensory responses in sensory cortex

大脑的一个核心功能是使用来自感官的信息来指导决策，计划和行动。在哺乳动物中，大脑皮层在这一过程中发挥着关键作用，它将原始的感官输入转化为具有意义的统一对象的感觉，并处理对象，动作和上下文之间的关系。阐明大脑皮层是如何组织的，对于理解大脑功能是必要的，并且已经成为数十年研究的主题。长期以来，人们认为不同的皮层区域具有不同的功能，因此感觉处理，决策或运动控制在不同的区域进行。但最近的研究发现，大脑皮层中的神经元可以对行为的许多方面做出反应：因此，以前被认为处理纯粹感官信息的部分大脑皮层实际上包含的神经元的反应反映了动物的决定和运动，以及它们的结果。这些非感官反应意味着大脑皮层的结构与我们想象的不同。因此，要了解皮层是如何工作的，我们需要找出这些非感觉反应是如何组织的。该项目将通过阐明感觉皮层中哪些类型的神经元可以产生非感觉反应以及它们的连接如何塑造这些反应来解决这一关键的知识缺口。具体来说，我们将测试以下假设：与罕见但关键的抑制性神经元相比，非感觉反应在更常见的兴奋性投射神经元类别中有所不同;非感觉反应取决于来自大脑其他区域的输入，这些区域参与决策和选择行动;非感觉神经元本身也以独特的方式连接回这些区域。达到这些目标需要观察和操纵大脑皮层的神经元活动，同时动物使用感觉输入来指导行动决定。两种强大的技术，双光子成像和光遗传学能够在单个神经元的水平上测量和操纵活动，我们将联合收割机与我们为小鼠开发的基于触摸的决策任务相结合。老鼠的胡须将受到一种刺激模式，如果它们识别出这种模式，就会舔来作为奖励;同时，我们将观察并干扰感觉皮层中接受胡须最直接输入的目标神经元的神经元活动。这些最先进的方法已经在我们的实验室中得到了测试。通过以这种方式阐明非感觉反应的组织，我们将对大脑皮层如何支持大脑功能提供新的见解。

A central function of the brain is to use information from the senses to guide decisions, plans and actions. In mammals, a key role in this process is played by the cerebral cortex, which transforms raw sensory input into the sense of a unified object with a meaning and processes relationships between objects, actions and context. Elucidating how the cortex is organised is necessary to understand brain function and has been the subject of decades of research. For a long time, it was thought that different cortical regions had separate functions, so that sensory processing, decision making or motor control were carried out in distinct regions. But recent work has discovered that neurons across the cortex can respond to many aspects of behaviour: thus, parts of cortex previously thought to process purely sensory information actually contain neurons whose responses reflect the animal's decisions and movements, and their outcomes. These non-sensory responses imply that the cortex is set up differently than was thought. Therefore, to understand how the cortex works, we need to find out how these non-sensory responses are organised. This project will tackle this key gap in knowledge by elucidating which types of neurons in sensory cortex can generate non-sensory responses and how their connections shape those responses. Specifically, we will test the hypotheses that non-sensory responses differ in the more common class of excitatory projection neurons as compared to rarer but crucial classes of inhibitory neurons; that non-sensory responses depend on inputs from other areas of the brain involved in making decisions and selecting actions; and that non-sensory neurons themselves also connect back to those areas in a distinct way. Reaching these aims requires observing and manipulating neuronal activity in the cortex while an animal is using sensory input to guide a decision to act. Two powerful techniques, two-photon imaging and optogenetics enable the measurement and manipulation of activity at the level of single neurons, and we will combine these techniques with a touch-based decision-making task that we have developed for mice. Mice will be given a pattern of stimulation to their whiskers and will lick for a reward if they recognise the pattern; meanwhile, we will observe and perturb neuronal activity in targeted sets of neurons within the part of sensory cortex that receives the most direct input from the whiskers. These state-of-the-art methods are already available and tested in our lab. By elucidating the organisation of non-sensory responses in this way, we will contribute new insight into how the cerebral cortex underpins brain function.