CORTICAL CIRCUITRY FOR TOP-DOWN SELECTION OF VISUAL INPUTS

描述(申请人提供)：大脑皮层的矩阵由重复回路组成，其局部、区域内连接占兴奋性突触的90%。当被激活时，这些电路产生正反馈，通过局部抑制来保持控制，并在选择输入和恢复来自外部世界的信号方面发挥作用。在小鼠初级视觉皮质(V1)内，不重叠的锥体细胞群通过水平网络在每个种群内连接，这些锥体细胞群具有不同的投射到较高视区Lm和AL。这些网络提供来自地形距离点的影响，并负责轮廓整合和图像分割。这种形式的语境加工受到注意、期望和知觉任务的影响，这表明来自腹侧流区(Lm)和背流区(AL)的反馈优先与V1内投射Lm和AL的水平网络相互作用。来自LM和AL的自上而下的影响可能分别是针对对象类别和时间语境的功能专门化的，并且与特定的水平V1网络的交互中断可能导致行为障碍。然而，缺乏上下文处理的本地网络和自上而下的路径之间相互作用的直接证据。在这里，我们建议研究：(1)投射Lm和AL的神经元是否形成单独的V1子网络；(2)来自背流区AL和腹侧流区的反馈是否优先与其接受前馈输入的子网络相互作用；(3)投射Lm的腹侧流子网络是否受到来自Lm的反馈输入的强烈抑制，而不是来自功能不同的背流区AL的反馈。我们建议通过对小鼠视皮层急性脑片中已识别的锥体神经元和中间神经元对进行全细胞膜片钳记录来研究这些问题，并使用亚细胞通道视紫红质辅助的电路映射来表征从背侧和腹侧流到不同兴奋性和抑制性V1子网络的反馈输入的特异性。 公共卫生相关性：初级视觉皮质的感觉处理受到注意力、期望和知觉任务的自上而下的强大影响。虽然人们普遍认为这些适应过程是由皮质区域之间的相互作用和高级皮质区域反馈连接对固有V1回路的调制决定的，但这些相互作用尚未被直接证实。这项拟议的研究将在小鼠的视皮层中解决这个问题，在那里，不同神经元类型、区域和功能流之间的突触联系可以比灵长类动物更容易被检查。如果成功，该项目将表明，自上而下的影响优先针对属于同一V1子网络的神经元，而跨功能不同的区域回路的兴奋性自上而下的影响更强烈地受到抑制的反对。所发现的突触电路可以实现能够重定向注意力的网络之间的切换。

DESCRIPTION (provided by applicant): The matrix of cerebral cortex consists of iterated circuits whose local, intra-areal connections account for 90% of excitatory synapses. When activated, these circuits generate positive feedback that is kept in check by local inhibition and plays a role in the selection of inputs and the restoration of signals from the outside world. Within mouse primary visual cortex (V1), non-overlapping groups of pyramidal cells with distinct projections to the higher visual areas LM and AL are connected within each population through horizontal networks. These networks provide influences from topographically distant points and are responsible for contour integration and image segmentation. This form of contextual processing is influenced by attention, expectation and perceptual task, suggesting that feedback from the ventral stream area, LM, and the dorsal stream area, AL, preferentially interacts with LM- and AL-projecting horizontal networks within V1. The top-down influences from LM and AL may be functionally specialized for object categories and temporal context, respectively, and disruption of interactions with specific horizontal V1 networks may lead to behavioral disorders. Direct evidence for interactions between context-processing local networks and top-down pathways, however, is lacking. Here, we propose to study whether: (1) LM- and AL-projecting neurons form separate V1 subnetworks, (2) feedback from the dorsal stream area, AL, and the ventral stream area, LM, preferentially interacts with the subnetwork from which it receives feedforward input, and (3) the LM-projecting ventral stream subnetwork is less strongly inhibited by feedback input from LM, than by feedback from the functionally different dorsal stream area, AL. We propose to study these questions by performing whole-cell patch clamp recordings form pairs of identified pyramidal neurons and interneurons in acute slices of mouse visual cortex, and to use subcellular channelrhodopsin-assisted circuit mapping to characterize the specificity of feedback inputs from dorsal and ventral streams to different excitatory and inhibitory V1 subnetworks. PUBLIC HEALTH RELEVANCE: Sensory processing in primary visual cortex is subject to powerful top-down influences by attention, expectation and perceptual task. Although it is widely accepted that these adaptive processes are determined by interactions between cortical areas and the modulation of intrinsic V1 circuits by feedback connections from higher cortical areas, these interactions have not been directly demonstrated. The proposed studies will address this problem in mouse visual cortex in which synaptic connections between different neuron types, areas, and functional streams can be examined more readily than in primates. If successful, the project will show that top-down influences are preferentially targeted to neurons that belong to the same V1 subnetwork and that excitatory top-down influences across functionally different interareal circuits are more strongly opposed by inhibition. The discovered synaptic circuits may enable switching between networks that enable redirecting attention.