CORTICAL CIRCUITRY FOR TOP-DOWN SELECTION OF VISUAL INPUTS

描述（申请人提供）：大脑皮层基质由迭代电路组成，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，并受到局部抑制的控制，在输入的选择和外部世界信号的恢复中发挥作用。在小鼠初级视觉皮层（V1）内，具有不同投射到高级视觉区域LM和AL的非重叠锥体细胞群通过水平网络在每个群体内连接。这些网络提供地形上遥远点的影响，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，表明来自腹侧流区（LM）和背侧流区（AL）的反馈优先与V1内LM和AL投射的水平网络相互作用。LM和AL的自上而下影响可能分别在功能上专门化于对象类别和时间背景，与特定水平V1网络的相互作用中断可能导致行为障碍。然而，上下文处理局部网络和自上而下途径之间相互作用的直接证据是缺乏的。在此，我们提出研究是否：(1) LM-和AL-投射神经元形成独立的V1子网络，(2)来自背流区域AL和腹流区域LM的反馈优先与接收前馈输入的子网络相互作用，(3)LM-投射的腹流子网络受到LM反馈输入的抑制程度低于功能不同的背流区域的反馈。AL.我们建议通过在小鼠视觉皮层急性切片中对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作图来表征来自背侧和腹侧流对不同兴奋性和抑制性V1子网络的反馈输入的特异性。

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.