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.