TY - JOUR T1 - Simulating Cortical Feedback Modulation as Changes in Excitation and Inhibition in a Cortical Circuit Model JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0208-16.2016 SP - ENEURO.0208-16.2016 AU - Edward Zagha AU - John D. Murray AU - David A. McCormick Y1 - 2016/08/11 UR - http://www.eneuro.org/content/early/2016/08/11/ENEURO.0208-16.2016.abstract N2 - Cortical feedback pathways are hypothesized to distribute context-dependent signals during flexible behavior. Recent experimental work has attempted to understand the mechanisms by which cortical feedback inputs modulate their target regions. Within the mouse whisker sensorimotor system, cortical feedback stimulation modulates spontaneous activity and sensory responsiveness, leading to enhanced sensory representations. However, the cellular mechanisms underlying these effects are currently unknown. In this study we use a simplified neural circuit model, which includes two recurrent excitatory populations and global inhibition, to simulate cortical modulation. First, we demonstrate how changes in the strengths of excitation and inhibition alter the input-output processing responses of our model. Second, we compare these responses with experimental findings from cortical feedback stimulation. Our analyses predict that enhanced inhibition underlies the changes in spontaneous and sensory evoked activity observed experimentally. More generally, these analyses provide a framework for relating cellular and synaptic properties to emergent circuit function and dynamic modulation.Significance Statement: Interactions with our surroundings are not fixed, but vary according to our internal goals and desires. Neuromodulation of neocortex is essential for this behavioral flexibility, by modulating the input-output properties of cortical circuits to match task demands. Experimental studies have demonstrated robust effects of neuromodulators on sensory responses, and a wide diversity of neuromodulatory actions on cellular targets. However, we still lack a robust framework for linking cellular properties to input-output properties of cortical circuits. To address this, we explore how a simplified circuit model can be modulated to produce a variety of functional circuits with different input-output properties. By comparing experimental and modeling data, we can make predictions about how cellular perturbations contribute to cortical modulations observed in vivo. ER -