FIGURE 7.

Glutamate released after activation of astrocytic TRPV4 enhances synaptic activity by signaling through type 1 mGluR. A and B, representative traces evoked by exposing cells to ATP (1 μm) are shown for WT and TRPV4KO astrocytes. C, comparison of ATP-evoked activation in WT and TRPV4KO astrocytes. D, a representative trace of 4αPDD-evoked mEPSCs in TRPV4KO hippocampal neurons with or without CPPG (50 μm). E, a representative trace of 4αPDD-evoked mEPSCs in TRPV4KO hippocampal neurons with or without MPEP (1 μm). F, comparison of mEPSC amplitude and frequency in cells exposed to MPEP, 4αPDD, or MPEP and 4αPDD. *. p < 0.01, Duncan's multiple range test (versus MPEP). #, p < 0.01, Duncan's multiple range test (versus MPEP+4αPDD). G, schematic representation of our findings. TRPV4⁺ astrocytes, shown by the blue color, are specifically localized in the brain; activation of TRPV4 in these astrocytes causes excitation in neighboring astrocytes through gap junctions and ATP release, shown as red arrows. These cells form a unit of excitatory astrocytes that release glutamate, shown as green arrows. The glutamate that is released signals through type 1 mGluRs at presynaptic sites to enhance neurotransmitter release.