The M1 antagonist pirenzepine suppresses heterosynaptic STD in the CA1 region

The effect of the muscarinic M1 and M2 antagonists (pirenzepine and gallamine) on heterosynaptic short-term depression (HSTD) of the CA1 population spike was studied in rat hippocampal slices. HSTD was evoked by a train of 30-50 pulses at 5 Hz (theta-like stimulation; TLS) delivered to the stratum oriens. Bath-applied pirenzepine (10(-6)-3 x 10(-6) M) significantly suppressed the magnitude of HSTD in the tested radiatum input (56 +/- 26% of control, p < 0.05). In contrast, gallamine (10(-6)-10(-5) M) did not suppress HSTD (102 +/- 7%). An enhancement of HSTD during application of eserine was also antagonized by pirenzepine (71 +/- 18%, p < 0.01), but not by gallamine (152 +/- 85%). These data suggest that acetylcholine synaptically released during TLS of the stratum oriens significantly contributes to HSTD in the CA1 region by activation of the M1 muscarinic receptor subtype.