CORTICAL CIRCUITRY FOR TOP-DOWN SELECTION OF VISUAL INPUTS

描述（由申请人提供）：大脑皮层的基质由迭代回路组成，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，并在输入的选择和来自外部世界的信号的恢复中发挥作用。在小鼠初级视觉皮层（V1）内，具有不同的投射到更高视觉区域LM和AL的锥体细胞的非重叠组通过水平网络在每个群体内连接。这些网络提供来自地形上远距离点的影响，并负责轮廓整合和图像分割。这种形式的上下文处理的影响，注意，期望和知觉任务，这表明腹侧流区，LM，背侧流区，AL，优先与LM和AL投射水平网络内V1的反馈。从LM和AL的自上而下的影响可能是功能专门的对象类别和时间的背景下，分别和特定的水平V1网络的相互作用的中断可能会导致行为障碍。然而，缺乏直接的证据，上下文处理的本地网络和自上而下的途径之间的相互作用。在此，我们建议研究：（1）LM投射神经元和AL投射神经元形成独立的V1子网络，（2）来自背侧流区AL和腹侧流区LM的反馈优先与其接收前馈输入的子网络相互作用，以及（3）LM投射腹侧流子网络不太强烈地受到来自LM的反馈输入的抑制，而不是通过功能不同的背流区AL的反馈。我们建议通过对小鼠视觉皮层急性切片中已识别的锥体神经元和中间神经元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：初级视皮层的感觉加工受到注意、期望和知觉任务的自上而下的影响。虽然人们普遍认为，这些自适应过程是由皮质区之间的相互作用和调制的内在V1电路的反馈连接从更高的皮质区，这些相互作用还没有被直接证明。拟议的研究将解决小鼠视觉皮层中的这个问题，其中不同神经元类型，区域和功能流之间的突触连接可以比灵长类动物更容易地检查。如果成功的话，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，并且在功能不同的interareal电路中，兴奋性自上而下的影响受到抑制的强烈反对。所发现的突触电路可以实现在网络之间的切换，从而能够重定向注意力。

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.