Anatomical and functional organization of inter-areal feedback circuits in the visual cortex, and their impact on neuronal responses

在哺乳动物的感觉皮层中，层次化组织的区域通过前馈相互连接。 和反馈(FB)电路。FF连接会产生更复杂的神经元反应特性 平行流中的区域专门处理特定刺激属性。相比之下，它的功能 FB的联系仍不清楚。在视觉皮质中，FB与自上而下的现象有关，如 作为视觉注意力、预测和视觉环境。然而，这些角色仍然是假设的，因为 缺乏选择性地标记、记录和操纵FB神经元活动的工具。因为FB电路无处不在 在大脑皮层，人类Fb连接和功能的异常与神经学有关 注意缺陷和自闭症等障碍，重要的是了解正常的FB连接和 在灵长类动物中的功能。在之前的资助中，我们开发了新的病毒和光遗传工具来选择性地标记FB 神经元，跟踪它们的输入和输出，记录和操纵它们在灵长类皮质中的活动。使用这些 工具，我们发现，从解剖学上讲，视觉区域V2和V1之间的Fb连接形成平行的路径，使 与V1神经元直接接触，将FF投射发送到V2，并链接V2和V1神经元，更喜欢类似的 视觉刺激功能。在功能上，我们发现V2FB向V1传递全局视觉空间信息，并且 控制V1细胞的感受野大小、环绕抑制和反应幅度。在这些研究中， 然而，我们没有理清与不同层相关的FB连接。解剖学的、功能性的和 理论证据表明，在每条平行的FB通路中，至少有两条，甚至更多， 从不同层产生并在不同层终止的FB组，可能具有不同的组织和功能。 我们的目标是了解与不同的FB连接相关的连接性和计算功能 每个FB流中的起始层和终止层。使用FB神经元的选择性标记，我们将 确定来自不同V2层的Fb对其V1端子层的不同贡献。此外， 利用狂犬病病毒介导的单突触输入示踪(TRIO)结合V1和V2的光学成像 功能图，我们将确定不同V1细胞的功能连通性和目标类型 层流特定的FB集合(目标1，2)。最后，我们将对不同的V2 FB集合的活动进行光遗传学操作 确定它们对V1神经元自发和视觉诱发反应(Aim3)的不同影响。 冲击力。这一提议将揭示V2和V1之间的层流特异性FB回路的解剖和功能。 这些信息将通知和完善FB函数的模型，影响人工系统的设计 以实现愿景，并提供对神经功能障碍的电路水平基础的新见解 与FB连接和功能异常(注意力障碍、自闭症)有关。

In the mammalian sensory cortex, hierarchically-organized areas are reciprocally connected via feedforward (FF) and feedback (FB) circuits. FF connections generate the more complex response properties of neurons in higher areas within parallel streams specialized in processing specific stimulus attributes. In contrast, the function of FB connections remains unknown. In the visual cortex, FB has been implicated in top-down phenomena, such as visual attention, prediction, and visual context. However, these roles have remained hypothetical, due to the lack of tools to selectively label, record, and manipulate the activity of FB neurons. As FB circuits are ubiquitous in cortex, and abnormalities in FB connectivity and function in humans have been linked to neurological disorders, such as attention deficits and autism, it is important to understand normal FB connectivity and function in primates. During prior funding, we developed novel viral and optogenetic tools to selectively label FB neurons, trace their inputs and outputs, and record and manipulate their activity in primate cortex. Using these tools, we found that, anatomically, FB connections between visual areas V2 and V1 form parallel pathways, make direct contacts with V1 neurons sending FF projections to V2, and link V2 and V1 neurons preferring similar visual stimulus features. Functionally, we found V2 FB conveys global visuo-spatial information to V1, and controls the receptive field size, surround suppression and response amplitude of V1 cells. In these studies, however, we did not disentangle FB connections related to different layers. Anatomical, functional and theoretical evidence indicates that within each parallel FB pathway there are at least two, and probably more, sets of FB arising from, and terminating in, different layers, likely having distinct organizations and functions. Our goal is to understand the connectivity and computational function of FB connections related to different layers of origin and termination within each FB stream. Using selective labeling of FB neurons, we will determine the differential contribution of FB from different V2 layers to their V1 termination layers. Moreover, using rabies-virus-mediated monosynaptic input tracing (TRIO) combined with optical imaging of V1 and V2 functional maps, we will determine the functional connectivity of, and the V1 cell types targeted by, different laminar-specific FB sets (Aims1,2). Finally, we will optogenetically manipulate the activity of distinct V2 FB sets to determine their differential impact on V1 neurons' spontaneous and visually-evoked responses (Aim3). Impact. This proposal will reveal the anatomy and function of laminar-specific FB circuits between V2 and V1. This information will inform and refine models of FB function, influence the design of artificial systems striving to achieve vision, and provide new insights into the circuit-level bases for neurological disorders that have been linked to abnormal FB connectivity and function (attention disorders, autism).