The role of astrocyte-neuron communication in network function and behavior.
Final Report Abstract
In my research project I investigated the astrocytic contribution to information processing and the astrocyte-neuron communication in the motor cortex of awake, behaving mice. My work employed a unique combination of behavioral, molecular, genetic, in vivo imaging, and data analysis techniques to provide a highly reproducible and controlled framework to my study. I trained mice to perform a visual detection task, during which the mice responded to the stimuli by initiating a running bout on a ball. Fully trained mice perform up to 300 trials per session and reach performance levels of up to 90% correct responses. The animals are injected with a mix of virus-mediated CaI2+ indicators AAV5:GfaABC1D-cyto-GCaMP6f and AAV1:Syn.jRGECO1a, which allow for dualcolor two-photon imaging of both cell types simultaneously. Immunohistochemistry helped optimize the chronic surgical preparation to minimize the impact on astrocytes, whose functioning is sensitive to interventions and inflammatory reactions. My preliminary results indicate that astrocytes exert behaviorally-relevant signals in mice. Astrocytes showed Ca2+ increases in runs triggered by visual stimuli, but did not respond to spontaneous running bouts. Although astrocytes respond in a stereotypic way to varying amplitudes of running bouts, they seem to be able to modify the strength of their response dependent on the perceptual information that is processed. I found astrocytes that responded more vigorously to stimuli at the animal's perceptual threshold. Moreover, my study suggests that behaviorally relevant communication between astrocytes and neurons exists. In trials, during which astrocytes responded in highly coordinated large-scale events (LSE), engaging all astrocytes in the visual field, neurons showed higher response rates. While a proportion of neurons increased its responses prior to an LSE, another proportion of neurons showed this modulation during or after an LSE. Further data analysis and the cellular/molecular dissection of the communication pathways between astrocytes and neurons will give insights into the causality of these correlations. Given astrocytes' major involvement in neurological and psychiatric disorders such as schizophrenia, bipolar disorder, and epilepsy, I believe that my basic research is critical for future studies on cellular and molecular pathways altered in these diseases.
Publications
- Imaging large-scale cellular activity in spinal cord of freely behaving mice. Nature Communications (2016) Apr 28; 7:11450
Sekiguchi KJ., Shekhtmeyster P., Merten K., Arena A., Cook D., Hoffman E., Ngo A., Nimmerjahn A.
(See online at https://doi.org/10.1038/ncomms11450) - Phosphatidylserine exposure controls viral innate immune responses by microglia. Neuron (2017) Feb 8; 93(3):574-586
Tufail Y., Cook D., Fourgeaud L., Powers C.J., Merten K., Clark C.L., Hoffman E., Ngo A., Sekiguchi K.J., O’Shea C. C., Lemke G., and Nimmerjahn A.
(See online at https://doi.org/10.1016/j.neuron.2016.12.021)
