PT - JOURNAL ARTICLE AU - Diego E. Pafundo AU - Mark A. Nicholas AU - Ruilin Zhang AU - Sandra J. Kuhlman TI - Top-Down-Mediated Facilitation in the Visual Cortex Is Gated by Subcortical Neuromodulation AID - 10.1523/JNEUROSCI.2909-15.2016 DP - 2016 Mar 09 TA - The Journal of Neuroscience PG - 2904--2914 VI - 36 IP - 10 4099 - http://www.jneurosci.org/content/36/10/2904.short 4100 - http://www.jneurosci.org/content/36/10/2904.full SO - J. Neurosci.2016 Mar 09; 36 AB - Response properties in primary sensory cortices are highly dependent on behavioral state. For example, the nucleus basalis of the forebrain plays a critical role in enhancing response properties of excitatory neurons in primary visual cortex (V1) during active exploration and learning. Given the strong reciprocal connections between hierarchically arranged cortical regions, how are increases in sensory response gain constrained to prevent runaway excitation? To explore this, we used in vivo two-photon guided cell-attached recording in conjunction with spatially restricted optogenetic photo-inhibition of higher-order visual cortex in mice. We found that the principle feedback projection to V1 originating from the lateral medial area (LM) facilitated visual responses in layer 2/3 excitatory neurons by ∼20%. This facilitation was reduced by half during basal forebrain activation due to differential response properties between LM and V1. Our results demonstrate that basal-forebrain-mediated increases in response gain are localized to V1 and are not propagated to LM and establish that subcortical modulation of visual cortex is regionally distinct.SIGNIFICANCE STATEMENT Reciprocal connectivity among brain regions is a prominent feature of all sensory cortices. In primary visual cortex (V1), top-down signals from association areas aid in context-dependent perception of visual scenes by altering the response properties of individual neurons. Sensory-evoked responses in V1 are also highly dependent on subcortical neuromodulation pathways that regulate brain state. Here, with cell-type-specific resolution, we addressed how corticocortical and subcortical pathways interact to regulate responsiveness of V1. Our results provide insight into the rules and conditions governing activity propagation in reciprocally connected networks.