LTP is impaired in the Schaffer collateral→CA1 pathway of hippocampal slices
from postpubescent (P26–P35), but not in prepubescent (P14–P18) double
Ras-GRF knock-out mice. HFS (two 100 Hz trains) was used to induce LTP in
hippocampal slices from P26–P35 (A) and
P14–P18 (B) wild-type and double Ras-GRF
[grf1/grf2(−/−)] mice. Both groups received two
trains of 100 Hz (1 s, 20 s delay) indicated by the arrow. The recorded fEPSP slope
is expressed as a percentage of baseline ± SEM, and data were pooled from each
group [closed circles, wild-type slices (A,
n = 15; B, n =
12); open circles, grf1/grf2(−/−) slices
(A, n = 13;
B, n = 10)]. Insets,
Representative fEPSPs recorded before (1) and after (2) HFS in wild-type and
grf1/grf2(−/−) slices. Calibration: horizontal, 10
ms; vertical, 1 mV. C, Hippocampal brain slices were
pretreated with buffer containing DMSO (closed boxes; n = 7), the
MEK inhibitor U0126 (20 μm; upward triangle; n = 7),
or the NMDAR inhibitor d-AP-5 (100 μm; downward triangle;
n = 4) before HFS stimulation. Data are expressed as in
A, B.
D, TBS was used in mature wild-type (closed
circles; n = 8) and
ras-grf1/grf2(−/−) slices (open circles;
n = 7); the recorded data are expressed as in
A–C. E,
Late-phase LTP was induced by four trains of 1 s, 100 Hz tetani (5 min delay) in
mature wild-type (closed circles; n = 8) and
grf1/grf2(−/−) slices (open circles;
n = 8); the data are displayed as in
A–C.