Role of astrocytes in translating neuronal activity to hemodynamic responses in visual cortex.


Schummers, J. 1, Yu, H. 1 and Sur, M. 1, 2

1Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge MA, USA
2Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge MA, USA

   

Astrocytes are a major class of non-neuronal cells in the brain that were long thought to act as a support network for neurons. Recently, evidence has accumulated for a more active role for astrocytes in brain function. Astrocytes have processes that are closely apposed to synapses, and they respond to a number of neurotransmitters, in large part via pathways that lead to the release of internal calcium. In addition, astrocytes contact vascular networks and can influence cerebral microcirculation. We have simultaneously imaged the activity of astrocytes and neurons with two-photon imaging of bulk loaded calcium indicators in primary visual cortex (V1) of the ferret. We have found that astrocytes have robust calcium responses to visual stimuli, which are delayed 2-4 seconds relative to neurons. The responses are sharply tuned for stimulus orientation and spatial frequency. Furthermore, their preferred orientation closely matches nearby neurons, and the organization of preferred orientation at pinwheel centers is equally precise for astroyctes. Astrocyte tuning is narrower than neuronal tuning, suggesting that astrocyte calcium responses have a high threshold for activation. Consistent with this suggestion, we discovered that astrocyte responses are remarkably sensitive to anesthetic (isoflurane) concentration, with a dramatic decrease in amplitude over a narrow range of anesthetic concentration, over which neuronal responses are only minimally reduced. We took advantage of this sensitivity to investigate the role of astrocyte calcium responses in hemodynamic responses. We obtained orientation preference maps with intrinsic signal optical imaging at anesthetic conditions that enabled us to selectively turn astrocyte responses on and off. By comparing responses at multiple wavelengths, we find that the delayed, visually-evoked, increase in blood flow is extremely sensitive to astrocyte activity levels. The blood flow response is reduced threefold when astrocytes calcium responses are reduced by high isoflurane. The early portion of hemodynamic signals is unaffected, suggesting a mechanistic link between the astrocyte calcium responses and blood flow increases. The mapping portion of the intrinsic signal is also dramatically reduced, suggesting that astrocytes are critical for translating local neuronal activity into localized increases in blood flow. The combination of highly organized response selectivity of astrocytes, and their role in regulating blood flow, likely contributes to the spatial localization of intrinsic signal responses.