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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Frank Kirchoff, Saarland University, Germany
- Second opponent: Professor Fritjof Helmchen, University of Zurich, Switzerland
- Third member and chair of the evaluation committee: Associate professor Anna Chaimani, University of Oslo
Chair of the Defence
Associate Professor Hua Hu, University of Oslo
Principal Supervisor
Researcher Wannan Tang, NTNU
Summary
Astrocytes support brain homeostasis, but they also participate in neural circuit function. This participation is closely linked to intracellular Ca2+ signaling, expressed as spatiotemporally diverse Ca2+ transients. The aim was to determine how whisker-related input and behavioral state (whisking and locomotion) shape astrocytic Ca2+ activity in mouse vibrissal primary somatosensory cortex (vS1), how local neuronal activity contributes to astrocytic Ca2+, and how impaired astrocytic Ca2+ signaling affects neuronal activity during behavior. In addition, we asked which membrane pathways can trigger astrocytic Ca2+ responses to neuronal activity.
Using in vivo two-photon imaging in layer 2/3 vS1 during tactile virtual-reality whisker stimulation, free whisking, and locomotion, we found that locomotion increased astrocytic Ca2+ event frequency and amplitude, and that whisker stimulation further elevated astrocytic activity during locomotion. When local neurons were chemogenetically silenced (GlyRα1AG), Ca2+ magnitude changed little, but astrocytic event onsets were delayed, indicating that local circuit activity mainly controls event timing.
To test how reduced astrocytic Ca2+ release influences activity during behavior, we studied Itpr2−/− (IP3R2 knockout) mice. Astrocytic Ca2+ transients were strongly y reduced but not completely abolished, in accordance with previous studies. Neuronal activity in vS1 was largely preserved, but locomotion-related neuronal modulation was reduced.
Finally, in acute hippocampal slices we identified membrane mechanisms for astrocytic responsiveness to neuronal activity. The Na+/Ca2+ exchanger (NCX) was required to initiate astrocytic Ca2+ responses, while P2X receptors amplified them.
Overall, astrocytic Ca2+ signaling is state dependent and temporally regulated, supported by intracellular release and membrane influx pathways. The results suggest that astrocytic Ca2+ signals sustain locomotion-linked modulation of neuronal activity.
Additional information
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