Download or read book Mechanisms Underlying State-dependent Modulation of Cortical Activity written by Sergio E. Arroyo and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The processing of information in cortical circuits is dynamic and varies widely across behavioral and cognitive states. In the cortex, sensory information from the periphery is transformed by a combination of local recurrent connections, interactions with other cortical areas, and inputs from several ascending neuromodulatory systems. However, the precise cellular mechanisms underlying state-dependent modulation of cortical circuits remain poorly understood. Here, I describe two approaches to address this question: an in vitro approach to study the impact of cholinergic signaling on cortical circuits, and an in vivo approach to investigate cellular mechanisms underlying modulation of visual responses in the awake, behaving mouse. Many lines of evidence suggest that the cholinergic system plays an important role in coordinating many large-scale changes in brain activity associated with behavioral state. To investigate how activation of cholinergic axons modulates cortical circuits, we developed methods to transduce cholinergic neurons in the basal forebrain with channelrhodopsin-2. This approach allowed us to selectively activate cholinergic terminals in the cortex in vitro and study (1) the cortical cell-types targeted by cholinergic axons and (2) the kinetics and synaptic properties of cholinergic signaling. To study the cellular mechanisms underlying state-dependent modulation of visual responses, we obtained whole-cell recordings from visual cortical neurons in the awake, behaving mouse. We characterized two cortical network states that were tightly correlated with distinct wakeful behavioral states: quiet wakefulness and locomotion. We demonstrated that subthreshold responses to visual stimulation were larger and more reliable during locomotion due to an increase in excitatory and inhibitory conductances and a shift in the stimulus-evoked reversal potential. Furthermore, by obtaining two simultaneous whole-cell recordings from visual cortical neurons, we were able to measure how correlated subthreshold activity was modulated by behavioral state and the patterns of excitatory and inhibitory synaptic inputs that generate these correlations. Together, these experiments provide insight into the cellular mechanisms that underlie state-dependent changes in cortical activity, sensory processing, and behavior.