Figure 5

Astrocytic glutamate released upon PAR1 activation targets GluN2A-containing synaptic NMDARs. A, Representative recording traces indicating NMDAR-dependent whole-cell currents measured from a CA1 pyramidal neuron induced by the treatment with TFLLR(for PAR1) or endothelin (for endothelin receptor), in the presence of GluN2A (ZnCl₂) or GluN2B-specific antagonist (RO25-6981). The arrow and dotted lines indicate the current responses before and after agonist treatments. B, Bar graph summarizing the averaged amplitudes of NMDAR-dependent currents induced by astrocytic glutamate (mean ± s.e.m). Numbers of tested slices from at least three independent mice are indicated within each bar. *, p < 0.05, unpaired two-tailed Student’s t-test. C, Upper: representative NMDAR-eEPSP responses (isolated by co-application of 20 μM CNQX and 5 μM bicuculline) measured from CA1 pyramidal neuron, before (1) and after (2) TFLLR treatment in the absence of MK-801, and before (3) and after (4) TFLLR treatment in the presence of MK-801. Gray traces indicate NMDAR-eEPSP before TFLLR application in each experimental condition. Lower: representative time course of the amplitude of NMDAR-eEPSPs from a single CA1 pyramidal neuron. Numbers (1) to (4) represent the same as those in the Upper section. D, Bar graph comparing normalized amplitudes of NMDAR-eEPSPs after TFLLR treatment with those before TFLLR treatment (% of control by TFLLR; mean ± s.e.m.). Numbers of tested slices from at least three independent mice are indicated within each bar. *, p < 0.05, unpaired two-tailed Student’s t-test.