(a,b) Systemic injection of scopolamine
(0.2 mg kg−1, i.p.), a
muscarinic acetylcholine receptor antagonist, completely prevented
LFS-induced LTD, whereas application of the nicotinic acetylcholine receptor
antagonist mecamylamine
(5 mg kg−1, i.p.) did
not affect LTD induction. Open triangle, i.p.; hash, intracerebroventricular
(i.c.v.). As summarized in (b) the EPSP decreased significantly to
72.0±4.4% in the vehicle control group and the mecamylamine group
(67.1±4.9%, n=4, P<0.05 compared with Pre,
P>0.05 compared with vehicle) but not in the scopolamine group
(96.5±6.4%, n=6, P>0.05 compared with Pre,
P<0.05 compared with vehicle); paired t and one-way
ANOVA-Tukey. (c,d) LFS-900-induced LTD was also significantly
reduced by treatment with the M1-selective mAChR antagonist pirenzepine (triangle,
50 nmol in 5 μl). As summarized in
(d), the EPSP decreased to 67.5±4.5% and 90.4±2.1%,
n=4, in vehicle- and pirenzepine-injected animals, respectively
(P<0.05 compared with Pre and between groups; t-test).
(e,f) Application of LFS-900 before the injection of
scopolamine
(triangle, 0.2 mg kg−1,
i.p.) induced robust LTD (71.7±7.2%, n=6,
P<0.05 compared with Pre; paired t).
(g,h) The acetylcholinesterase inhibitor donepezil lowered the threshold to
induce LTD. (g) The application of weak LFS (bar, LFS-300; 300
high-intensity pulses at 1 Hz) induced a transient synaptic
depression in vehicle-injected animals (triangle), whereas the same protocol
triggered a robust and stable LTD after acute injection of donepezil
(1 mg kg−1,
subcutaneously). (h) Veh: 101.8±6.3%; donepezil: 70.5±7.1% at
3 h after LFS. *P<0.05, t-test, n=4
per group. Values are mean±s.e.m. Calibration bars: vertical,
2 mV; horizontal, 10 ms.