Figure 1. Clamping astrocytic Ca²⁺ blocks LTP at nearby synapses in a D-serine-dependent manner.

a, Experimental arrangement: ip, intracellular patch-pipette; ep, extracellular pipette; green line, Schaffer collaterals.

b, A typical patched astrocyte (Alexa Fluor 594, ~120 μm stack fusion); ep and ip as in a; bv, blood vessel; escape of Alexa to neighbouring cells can be seen; inset: DIC at lower magnification.

c, LTP of AMPAR fEPSPs in control conditions, with (n = 23, green) or without (n = 29, grey) astrocyte patched. Arrow, HFS onset; traces, characteristic AMPAR fEPSPs before (black) and after (grey) LTP induction; notations apply in c-e.

d, Clamping astrocytic Ca²⁺ (0.2 mM OGB-1, 0.45 mM EGTA, 0.14 mM CaCl₂) abolishes local LTP (n = 19, orange) whereas 10 μM D-serine rescues it (n = 10, green).

e, LTP in 10 μM D-serine (163 ± 12%, n = 8, green; no astrocyte patched) is no different from that in control (Fig. 1c) suggesting saturation of either the NMDAR co-agonist site or the downstream induction mechanism. 50 μM APV completely blocks LTP (n = 12, orange).

f, Summary for experiments in c-e, as indicated. Bars, mean ± s.e.m for fEPSPs measured 25-30 min post-HFS relative to baseline. ***, p < 0.005 (one-population t-test); ⁺⁺⁺, p < 0.002 (two-population t-test).