UC Riverside

In addition to synaptic communication between neurons, there is now strong evidence for neuron-to-astrocyte receptor signaling in the brain. During trains of action potentials or repetitive stimulation, neurotransmitter spills out of the synapse to activate astrocytic Gq protein-coupled receptors (Gq GPCRs). To date, very little is known about the ability of astrocytic receptors to exhibit plasticity as a result of long-term changes in neuronal firing rates. Here we describe for the first time bidirectional scaling of astrocytic group 1 metabotropic glutamate receptor (mGluR) signaling in acute mouse hippocampal slices on a rapid timescale following either long-term blockade or increase in neuronal synaptic transmission. Plasticity of astrocytic mGluRs was measured by recording changes in spontaneous and evoked astrocyte Ca2+ elevations in both astrocytic soma as well as fine processes. In response to 4 to 6 hour blockade of CA3-CA1 neurotransmission, the following changes in astrocyte Ca2+ signaling were observed: 1) a significant increase in the percentage of astrocytes in the slice population exhibiting spontaneous Ca2+ elevations; 2) significantly faster rise times of the spontaneous Ca2+ transients; 3) a significant increase in response probability to the group I mGluR agonist; 4) significantly faster rise times of evoked Ca2+ responses; 5) significantly shorter response latencies of evoked Ca2+ responses in astrocyte microdomains; and 6) a dose-dependent shift in astrocytic responses to DHPG in TTX vs. control incubated slices. In response to 4 to 6 hour elevation of CA3-CA1 neurotransmission, the opposite effects on the previous parameters were observed. Further study using transgenic mice expressing a novel Gq GPCR suggested that the changes observed in astrocytic group I mGluR Ca2+ signaling were due to changes in expression of the group I mGluRs in astrocytes, while the intracellular signaling pathway activated by the Gq GPCRs remained unchanged. This study introduces a sensitive assay for recording changes in astrocytic Gq GPCR expression levels, and the results demonstrate active astrocytic detection of basal and elevated frequencies of neuronal action potentials that lie within a physiological range.