Intracellular Astrocyte Calcium WavesIn SituIncrease the Frequency of Spontaneous AMPA Receptor Currents in CA1 Pyramidal Neurons

Open Access
Publisher Website
Google Scholar
Abstract
Spontaneous neurotransmitter release and activation of group I metabotropic glutamate receptors (mGluRs) each play a role in the plasticity of neuronal synapses. Astrocytes may contribute to short- and long-term synaptic changes by signaling to neurons via these processes. Spontaneous whole-cell AMPA receptor (AMPAR) currents were recorded in CA1 pyramidal cellsin situwhile evoking Ca2+increases in the adjacent stratum radiatum astrocytes by uncaging IP3. Whole-cell patch clamp was used to deliver caged IP3and the Ca2+indicator dye Oregon green BAPTA-1 to astrocytes. Neurons were patch-clamped and filled with Alexa 568 hydrazide dye to visualize their morphological relationship to the astrocyte. On uncaging of IP3, astrocyte Ca2+responses reliably propagated as a wave into the very fine distal processes, synchronizing Ca2+activity within astrocyte microdomains. The intracellular astrocyte Ca2+wave coincided with a significant increase in the frequency of AMPA spontaneous EPSCs, but with no change in their kinetics. AMPAR current amplitudes were increased as well, but not significantly (p= 0.06). The increased frequency of AMPAR currents was sensitive to the group I mGluR antagonistsLY367385and 2-methyl-6-(phenylethynyl)-pyridine, suggesting that (1) astrocytes released glutamate in response to IP3uncaging, and (2) glutamate released by astrocytes activated group I mGluRs to facilitate the release of glutamate from excitatory neuronal presynaptic boutons. These results extend previous studies, which have shown astrocyte modulation of neuronal activityin vitroand suggest that astrocyte-to-neuron signaling in intact tissue may contribute to synaptic plasticity.