Alexander Gourine & Jeffrey Smith Collaboration
Title: How astrocytes shape the activity of vital neuronal circuits?
Astrocytes are the most abundant type of brain glial cells. Rapidly accumulating evidence indicates that their role in the brain is by no means limited to just providing structural and metabolic support to neurons as was thought previously. Astrocytes are closely associated with cerebral blood vessels – all penetrating and intracerebral arterioles and capillaries are enwrapped by astrocytic endfeet. There is strong evidence that by regulating cerebrovascular tone astrocytes control local blood supply to support metabolic demands of brain areas with increased activity. A single astrocyte may enwrap several neuronal somata and make contacts with tens of thousands of individual synapses potentially regulating synaptic strength and information processing. However, direct evidence demonstrating the active role of astrocytes in shaping activities of neuronal networks is still missing.
We will isolate and study brainstem respiratory circuits using in vitro and in situ models. Respiratory networks even in dramatically reduced preparations (such as brainstem slices in vitro) generate identifiable motor (respiratory) output while also allowing experimental control of the brain microenvironment and therefore are by far better in comparison to other experimental models of CNS neural circuits. We shall use state of the art imaging and optogenetic tools to study the importance and functional significance of the glial microenvironment in shaping the normal activity of CNS respiratory circuits. We aim to identify fundamental mechanisms of how neural circuits embedded into astrocytic networks interact and are controlled in relation to each other to generate instant changes in motor control to support prevailing behavioral demands.