Astrocytic mitochondria in adult mouse brain slices show spontaneous calcium influx events with unique properties Academic Article uri icon

abstract

  • Astrocytes govern critical aspects of brain function via spontaneous calcium signals in their soma and processes. A significant proportion of these spontaneous astrocytic calcium events are associated with mitochondria, however, the extent, sources, or kinetics of astrocytic mitochondrial calcium influx have not been studied in the adult mouse brain. To measure calcium influx into astrocytic mitochondria in situ, we generated an adeno-associated virus (AAV) with the astrocyte-specific GfaABC1D promoter driving expression of the genetically encoded calcium indicator, GCaMP6f tagged to mito7, a mitochondrial matrix targeted signal sequence. Using this construct, we observed AAV-mediated expression of GCaMP6f in adult mouse astrocytic mitochondria that co-localized with MitoTracker deep red (MTDR) in the dorsolateral striatum (DLS) and in the hippocampal stratum radiatum (HPC). Astrocytic mitochondria co-labeled with MTDR and GCaMP6f displayed robust, spontaneous calcium influx events in situ, with subcellular differences in calcium influx kinetics between somatic, branch, and branchlet mitochondria, and inter-regional differences between mitochondria in DLS and HPC astrocytes. Calcium influx into astrocytic mitochondria was strongly dependent on endoplasmic reticulum calcium stores, but did not require the mitochondrial calcium uniporter, MCU. Exposure to either glutamate, D1 or D2 dopamine receptor agonists increased calcium influx in some mitochondria, while simultaneously decreasing calcium influx in other mitochondria from the same astrocyte. These findings show that astrocytic mitochondria possess unique properties with regard to their subcellular morphology, mechanisms of calcium influx, and responses to neurotransmitter receptor agonists. Our results have important implications for understanding the role of astrocytic mitochondria during pathological processes.

altmetric score

  • 1.25

author list (cited authors)

  • Huntington, T. E., & Srinivasan, R.

citation count

  • 1

publication date

  • February 2021