LTP and phosphorylation of Akt and GSK-3β are reduced in juvenile <i>NesCreIrs2KO</i> mice.

<p><b>A</b>: LTP induced by a single TBS in slices with intact inhibitory synaptic transmission was significantly reduced in juvenile <i>NesCreIrs2KO</i> mice (−/−; average EPSP slope change: 128±11%, N = 5, n = 7) compared to values obtained from littermate controls (+/+; average EPSP slope change: 160±9%, N = 7, n = 7, p<0.05), 60 min following induction. <b>B</b>: Representative EPSP traces (average of 4 consecutive sweeps) from individual experiments taken immediately prior to TBS, and following 60 min of LTP in both control (+/+) and <i>NesCreIrs2KO</i> (−/−) mice. <b>C</b>: Immunoblot analysis from CA1 lysates showing that neither the total level of p38MAPK nor the amount of phosphorylated p38MAPK (Thr180/Tyr182) are altered by brain-deletion of IRS-2 in <i>NesCreIrs2KO</i> (−/−; 102±8%) mice compared with control littermates (+/+; 100±14%, n = 5–7; p = 0.91). The bar diagram on the right shows a summary of the data obtained from 5–7 mice per experimental group. <b>D</b>: Immunoblot analysis from CA1 specific lysates showing that neither the total level of p42/44 MAPK (ERK) nor the amount of ERK phosphorylated at Thr202 and Tyr204 are altered by brain-deletion of IRS-2 in <i>NesCreIrs2KO</i> mice. For p42 MAPK: +/+ 100±6.5%; −/− 94.8±5.5%; n = 5; p = 0.56. For p44 MAPK: +/+ 100±6.4%; −/− 101.5±4.7%; n = 5; p = 0.86. <b>E</b>: Immunoblot analysis from CA1 lysates showing reduced Akt/protein kinase B phosphorylation levels at Thr308 and Ser473 in <i>NesCreIrs2KO</i> mice (−/−; Ser473: 74±8.%; Thr308: 61±9%, n = 7) compared to controls (+/+; Ser473: 100±8%; Thr308: 100±9%, n = 7; p = 0.04 for Ser473, p = 0.01 for Thr308). The bar diagram on the right shows a summary of the data obtained from 7 mice per experimental group. <b>F</b>: Immunoblot analysis from CA1 lysates showing reduced phoshosphorylation of GSK-3β at Ser9 in <i>NesCreIrs2KO</i> mice (−/−; 48±10%, n = 5) compared to controls (+/+; 100±10%, n = 5; p = 0.007). The bar diagram on the right shows a summary of the data obtained from 5 mice per experimental group. Data are expressed as mean ± SEM. *p<0.05; **p<0.01 (unpaired t-test).