Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down Syndrome

Figure 5

Aβ oligomers inhibit 4xHFS-induced LTP in euploid slices (but not Ts65Dn slices) and rPrP suppresses this inhibition. (a, b) Normalized fEPSP slopes in the presence or absence of Aβ oligomers alone or Aβ mixture with rPrP from euploid control-derived slices (a) or Ts65Dn-derived slices (b). Magnification of the final 10 minutes of recording. Colored lines represent the calculated mean fEPSP slopes for the last 10 minutes of recording. (c, d) Mean fEPSP slopes during the last 10 min of fEPSP recordings derived from data shown in panels (a) and (b), respectively. In Ts65Dn-derived slices, which already shows a deficit in 4xHFS-induced L-LTP when compared to euploid controls, Aβ oligomers had no further effect on L-LTP. rPrP rescued Aβ oligomer-induced inhibition 4xHFS-induced LTP in control slice; however, rPrP alone had no effect on 4xHFS-induced LTP in Ts65Dn-derived slices. (e) Shows that the levels of LTP in untreated control slices is significantly larger than the levels of LTP observed in Ts65Dn mouse slices under any treatment. (f) Relative decrease in 4xHFS-induced LTP due to Aβ oligomer-induced inhibition. Euploid control slices showed greater inhibition due to Aβ oligomers when compared to Ts65Dn-derived slices. , , and is represented by , , , respectively. Number of slices (animals) for control (aCSF (), Aβ (), rPrP (), and Aβ mixture with rPrP ()) and Ts65Dn (aCSF (), Aβ (), rPrP (), and Aβ mixture with rPrP ()). Error bars represent SEM. Arrows indicates LTP induction (4xHFS; with a 5 min intertrain intervals), representative traces show synaptic response during baseline (1) and at end of recording (2). Scale bars represent 1 mV (horizontal) and 10 ms (vertical). Horizontal black bar indicate aCSF, Aβ, rPrP, or Aβ mixture with rPrP.

(a)

(b)

(c)

(d)

(e)

(f)