Fig. 6.

Age- and region-dependent changes in plasticity in the HD mouse. a, Left, The magnitude of LTP expressed at transgenic CA1 synapses over three age ranges is compared with that seen in the control slices. LTP is significantly impaired in transgenic slices from 5 weeks onward [5–6 weeks, 26.2 ± 3.9% (n = 5); 7–9 weeks, 30.9 ± 7.2% (n = 5); ≥10 weeks, 22.9 ± 4.54 (n = 7); controls slices, 56.5 ± 6.6% (n = 13); level of significance determined using Bonferroni multiple comparisons test]. Right, Lasting activity-dependent synaptic depression is enhanced in transgenic slices from 5 weeks onward [5–6 weeks, −38.8 ± 5.5% (n = 5); 7–9 weeks, −47.4 ± 11.4% (n = 5); ≥10 weeks, −51.6 ± 4.2% (n = 8); control slices, −7.0 ± 2.9].b, The induction of LTP at granule cell synapses is age-dependent in transgenic mice. Top, LTP was induced in both control and transgenic slices in animals aged 4–7 weeks [57.8 ± 15.7% (n = 8) and 30.0 ± 9.4% (n = 11), respectively; p< 0.05]. Bottom, LTP is absent at transgenic granule cell synapses in animals aged ≥12 weeks [68.2 ± 13.4% (n = 5) and 15.8 ± 5.4% (n = 7) in control and transgenic slices, respectively; p < 0.01]. c, The induction of LTD at transgenic CA1 synapses is NMDA receptor-dependent. Low-frequency conditioning (open bar) failed to induce LTD in the presence of 25 μmd-AP5 (filled bar) (1.8 ± 0.1%, 3 slices from 3 animals; measured 1 hr after conditioning). Subsequent low-frequency conditioning after washout of AP5 successfully induced LTD (−31.8 ± 0.2%; p < 0.01, pairedt test).