Fig. 1.

I-LTD induction requires both CB1R activation and spontaneous activity of interneurons in the hippocampus. (A) Reducing spontaneous IPSCs with a low dose of TTX (10 nM) blocked I-LTD induced by TBS even while maintaining .067 Hz of test stimulation after TBS. The loss of I-LTD in 10 nM TTX could be rescued by bursts of afferent activity with extracellular stimulation. mGluR-I antagonists (4 μM MPEP and 100 μM LY367385) were washed in at the time of I-LTD induction. (B) Ten minutes of rescue stimulation alone (as in A) does not induce I-LTD. (C) Application of the CB1R agonist WIN (5 μM, 25 min) chased with the CB1R antagonist SR 141716 (5 μM) induced a lasting depression of fIPSPs under normal recording conditions. Similar to I-LTD, this depression was abolished in 10 nM TTX. (D) In experiments where two independent pathways were being stimulated, long-term depression of fIPSPs, blocked by 10 nM TTX in one pathway, could be rescued in the other pathway by burst stimulation of afferents (as in A, indicated by solid line, applied during final 10 min in WIN). Averaged sample traces taken at times indicated by numbers are shown above each panel.