A fundamental question in neuroscience is whether we can causally link distinct patterns of defined circuit elements with behavior. A mechanistic understanding of patterned activity will take into account the individual neurons and their synaptic interactions within distributed networks spanning multiple regions. We propose here to use genetically targeted switches of pyramidal neurons and whole-brain functional imaging to study the dynamics of distributed functional networks. Recent work has revealed that optogenetic strategies, using activation of channelrhodopsin-2 (ChR2), a light-gated cation channel, can be employed to drive the functional magnetic resonance imaging (fMRI) blood oxygenation-level dependent response in the rodent. Leveraging optogenetic fMRI we have shown that fMRI tracks optically evoked neural activity; further, we as well as others have shown that activity is observed locally and downstream of the light activated target. In this proposal we will use whole-brain high-resolution fMRI in awake mice combined with optogenetic activation (ChR2) of pyramidal neurons to assess the impact of causal manipulations on distributed brain network responses. Specifically, we will use the barrel field in primary somatosensory cortex (SI) to study the functional-anatomy of the mystacial vibrissa somatosensory system. We will focus on the following issues: (1) Examine whether optically-driven SI activity can be used to reveal somatotopic organization in regions connected to SI; (2) Examine the brain-wide functional-anatomy of SI optically driven activity by characterizing fMRI responses in relation to anatomical connections and neural plasticity; (3) Use regions identified with optically driven fMRI responses to focus our electrophysiological and anatomical experiments. We expect that the proposed research will contribute to our understanding of functional connections between regions, and highlight response properties in parts of the network unstudied so far.
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