The M1 antagonist pirenzepine suppresses heterosynaptic STD in the CA1 region

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Abstract
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 (10−4-3 x 10−4 M) significantly suppressed the magnitude of HSTD in the tested radiatum input (56 ± 26% of control, p < 0.05). In contrast, gallamine (10−4-10−5 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.

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