Project SummaryAstrocytes are major constituents of neural circuits, comprising nearly one third of cells in gray matter. Theyinteract with neural circuit elements both physically and functionally via bidirectional signaling with neurons.Astrocytes respond to neural activity in large part by increasing intracellular calcium on multiple spatial andtemporal scales, via a variety of mechanisms. These calcium signals are a necessary component of the signalingpathway for many forms of astrocyte signaling back to neurons. Thus, an understanding of the functional role ofastrocytes in neural circuit function requires a quantitative elucidation of the spatial and temporal neural activitypatterns that elicit calcium signaling in astrocytes, and the integration of subcellular calcium signals withinindividual astrocytes. We propose to define these relationships by making use of the precise neural circuitorganization in ferret visual cortex. Ferret visual cortex is functionally organized into precise orientation columns,such that different orientations of visual stimulation produce spatially distinct activity patterns in neural circuits,which enables precise experimental control of the spatial patterns of neural activity. We will specifically address1) the subcellular compartmentalization of astrocyte responses to different stimulus orientations, 2) thesubcellular organization of responses under precise control of stimulus amplitude and duration and 3) the impactof the different neural activity patterns underlying different brain states on astrocyte calcium responses. Togetherthese studies will provide unprecedented quantitative insight into 1) the spatial patterns of neural activity that arerequired to activate astrocyte calcium signaling, 2) the temporal integration of the magnitude of neural activitythat are necessary to activate astrocyte calcium signaling and 3) the brain states that promote astrocyteresponses to neural activity. Quantitative definitions of these rules will provide an important baseline againstwhich to compare and test the role of astrocytes in the brain dysfunction of pathological states related to diseasesof mental health.
