"Intelligent behavior depends on the ability to generate flexible, context-dependent actions. In the brain it is known that sensory cortices receive the top-down signal from higher cortical areas, which provides ""executive control"" and specifies the context or rules currently in effect. However, little is known about how this top-down signal is integrated by neurons and eventually influences the behavior of animals. Of special importance for this integration are the distal apical dendrites of cortical pyramidal neurons because top-down fibers target layer 1 of the cortex which are densely innervated by these structures. Furthermore, pyramidal neurons have specialized molecular machinery in just this region of the cell that dominate the integrative process and dictate firing output. We therefore hypothesize that optically manipulating the dendritic activity should influence the behavior of awake animals. We will test this hypothesis by measuring how the dendritic activity is modulated by the animal's behavior (Aim 1) and how active manipulation of dendritic activity influences the behavior (Aim 2). Specifically, we will image and optogenetically manipulate the calcium activity of the apical tuft dendrite of layer 5 pyramidal neurons by targeting light activatable proteins to the dendrites. While animals perform a context-dependent task, e.g. licking or withholding licking based on the context in which a tactile stimulus is given to their limbs, we will compare the effects of light-based activation and inactivation of the dendrites. The host laboratory has recently developed the fiberoptic periscope system that has huge potential to reveal the contribution of a specific dendritic region to the large network activity. Through combined use of fiberoptic system, optogenetic technique and well-characterized behavior, we hope to provide important new insight into the cellular mechanism of the cognitive/sensorimotor interface underlying flexible behavior."
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