Abstract
Astrocyte Gq GPCR and IP3 receptor-dependent Ca2+ elevations occur spontaneously in situ and in vivo. These events vary considerably in size, often remaining confined to small territories of astrocyte processes called "microdomains" and sometimes propagating over longer distances that can include the soma. It has remained unclear whether these events are driven by constitutive (basal) GPCR signaling activity, neuronal action potential-dependent or quantal vesicular release, or some combination of these mechanisms. Here, we applied manipulations to increase or inhibit neuronal vesicular neurotransmitter release together with low-level stimulation of Schaffer collaterals in acute mouse hippocampal slices in an effort to determine the mechanisms underlying spontaneous astrocyte Ca2+ events. We found no significant change in spontaneous microdomain astrocyte Ca2+ elevations when neuronal action potentials were significantly enhanced or blocked. The astrocyte Ca2+ activity was also not affected by inhibitors of group I mGluRs. However, blockade of miniature neurotransmitter release using Bafilomycin A1 significantly reduced the frequency of microdomain astrocyte Ca2+ elevations. We then tested whether astrocyte Ca2+ microdomains can be evoked by low intensity SC stimulation. Importantly, microdomains could not be reproduced even using single, low intensity pulses to the SCs at a minimum distance from the astrocyte. Evoked astrocyte Ca2+ responses most often included the cell soma, were reduced by group I mGluR antagonists, and were larger in size compared to spontaneous Ca2+ microdomains. Overall, our findings suggest that spontaneous microdomain astrocyte Ca2+ elevations are not driven by neuronal action potentials but require quantal release of neurotransmitter which cannot be replicated by stimulation of Schaffer collaterals.
Original language | English (US) |
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Pages (from-to) | 1-16 |
Number of pages | 16 |
Journal | Cell Calcium |
Volume | 55 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2014 |
Externally published | Yes |
Keywords
- Bafilomycin A1
- Calcium
- Group I mGluRs
- MEPSC