Figure 5. Aβ facilitates the induction of muscarinic receptor-independent LTD by weak low-frequency stimulation.

(a,b) The application of weak LFS (bar, LFS-300; 300 high-intensity pulses at 1 Hz) triggered a robust and stable LTD after acute i.c.v. injection (hash) of 160 pmol Aβ_1–42 but not vehicle or the reverse peptide Aβ_42–1 (Aβ reverse). This dose of Aβ_1–42 did not affect baseline synaptic transmission in the absence of LFS-300 (Aβ no LFS). Data for soluble and protofibril Aβ are combined and some animals had an additional separate i.c.v. injection of 5 μl vehicle 15 min before Aβ. As summarized in (b) at 3 h the EPSP measured 93.3±3.6% in controls (n=8, P>0.05 compared with Pre; paired t), 69.9±3.8% in Aβ-injected rats (n=10, P<0.05 compared with Pre and vehicle group; paired t and one-way ANOVA-Tukey) and 97.3±4.3% in reverse peptide (n=4, P>0.05 compared with Pre). Injection of Aβ_1–42 (160 pmol, i.c.v.) did not affect baseline synaptic transmission (102.6±1.6% at 3 h, n=7, P>0.05 compared with Pre). (c,d) Aβ_1–42, when administered 15 min after LFS-300 did not facilitate LTD. As summarized in (d) the EPSP was not significantly decreased at 3 h post LFS-300 (92.2 ±8.3%, n=5, P>0.05 compared with Pre; paired t). (e,f) In animals pretreated with scopolamine at the dose (open triangle; 0.2 mg kg⁻¹, i.p.) that completely blocked LFS-induced LTD (see Fig. 2a,b), application of LFS-300 30 min after i.c.v. injection of vehicle did not induce LTD, whereas application of LFS-300 30 min after i.c.v. injection of soluble Aβ_1–42 induced a robust and stable LTD. As summarized in (f), at 3 h the EPSP measured 102.2±6.6% in the scopolamine+vehicle group (n=4, P>0.05 compared with Pre; paired t) and 71.2±5.8% in the scopolamine+Aβ group (n=6, P<0.05 compared with Pre or scopolamine+vehicle group; t-tests). Values are mean±s.e.m. Calibration: vertical, 2 mV; horizontal, 10 ms.