| First Author | Mehina EMF | Year | 2017 |
| Journal | J Neurosci | Volume | 37 |
| Issue | 34 | Pages | 8150-8165 |
| PubMed ID | 28733356 | Mgi Jnum | J:249994 |
| Mgi Id | MGI:6092894 | Doi | 10.1523/JNEUROSCI.0239-17.2017 |
| Citation | Mehina EMF, et al. (2017) Steady-State Free Ca(2+) in Astrocytes Is Decreased by Experience and Impacts Arteriole Tone. J Neurosci 37(34):8150-8165 |
| abstractText | Astrocytes can control basal synaptic strength and arteriole tone via their resting Ca(2+) activity. However, whether resting astrocyte Ca(2+) can adjust to a new steady-state level, with an impact on surrounding brain cells, remains unknown. Using two-photon Ca(2+) imaging in male rat acute brain slices of the somatosensory neocortex, we found that theta burst neural activity produced an unexpected long-lasting reduction in astrocyte free Ca(2+) in the soma and endfeet. The drop in intracellular Ca(2+) was attenuated by antagonists targeting multiple ionotropic and metabotropic glutamate receptors, and intracellular cascades involved Ca(2+) stores and nitric oxide. The reduction in astrocyte endfoot Ca(2+) was coincident with an increase in arteriole tone, and both the Ca(2+) drop and the tone change were prevented by an NMDA receptor antagonist. Astrocyte patch-clamp experiments verified that the glutamate receptors in question were located on astrocytes and that Ca(2+) changes within astrocytes were responsible for the long-lasting change in arteriole diameter caused by theta burst neural activity. In astrocytes from animals that lived in an enriched environment, we measured a relatively lower resting Ca(2+) level that occluded any further drop in Ca(2+) in response to theta burst activity. These data suggest that electrically evoked patterns of neural activity or natural experience can adjust steady-state resting astrocyte Ca(2+) and that the effect has an impact on basal arteriole diameter.SIGNIFICANCE STATEMENT The field of astrocyte-neuron and astrocyte-arteriole interactions is currently in a state of refinement. Experimental evidence ex vivo suggests that direct manipulation of astrocyte-free Ca(2+) regulates synaptic signaling and local blood flow control; however, in vivo experiments fail to link synaptically evoked astrocyte Ca(2+) transients and immediate changes to various astrocyte-mediated processes. To clarify this discrepancy, we examined a different aspect of astrocyte Ca(2+): the resting, steady-state free Ca(2+) of astrocytes, its modulation, and its potential role in the tonic regulation of surrounding brain cells. We found that ex vivo or in vivo neural activity induced a long-lasting reduction in resting free astrocyte Ca(2+) and that this phenomenon changed arteriole tone. |
