Adipose tissue weights after 12 weeks of dietary treatment.

<p>Data are means ± SE, n = 18–19. Visceral adipose tissue (VAT) was collected from epididymis and, subcutaneous adipose tissue SAT was collected from the gluteal region. Symbols indicate differences, <i>P</i> < 0.05: (a) different from AL (*), (b) different from CURAL (#).</p

Estimated food intake over a span of 12 weeks of dietary treatment.

<p>Data are means ±SEM, n = 18–19. Food intake was measured at 4, 8 and 12 weeks of dietary treatment. Symbols indicate differences, <i>P</i> < 0.05: (a) different from AL (*).</p

Redox state.

<p>Concentration of (A) reduced glutathione, (B) GSH/GSSG and (C) oxidized glutathione in erythrocytes after 8 weeks of dietary treatment. Bars represent means ± SE, n = 8–10. Symbols indicate differences, <i>P</i> < 0.05: (a) different from AL (*), (c) different from CR (†).</p

Body weight over a span of 12 weeks of dietary treatment.

<p>Data are means ±SEM, n = 18–19, for: AL, base diet fed ad libitum; CR, base diet restricted to 70% AL, CURAL, curcumin in base diet fed AL. Symbols indicate differences, <i>P</i> < 0.05: (a) different from AL (*), (b) different from CURAL (#).</p

Serum concentration of C-reactive protein as a function of diet.

<p>Data represent the average of measurements at 8 and 12 weeks of treatment. Bars represent means +SE, n = 8–10. (a) <i>P</i><0.05 when compared with AL (*).</p

A role for calcium-permeable AMPA receptors in synaptic plasticity and learning.

A central concept in the field of learning and memory is that NMDARs are essential for synaptic plasticity and memory formation. Surprisingly then, multiple studies have found that behavioral experience can reduce or eliminate the contribution of these receptors to learning. The cellular mechanisms that mediate learning in the absence of NMDAR activation are currently unknown. To address this issue, we examined the contribution of Ca(2+)-permeable AMPARs to learning and plasticity in the hippocampus. Mutant mice were engineered with a conditional genetic deletion of GluR2 in the CA1 region of the hippocampus (GluR2-cKO mice). Electrophysiology experiments in these animals revealed a novel form of long-term potentiation (LTP) that was independent of NMDARs and mediated by GluR2-lacking Ca(2+)-permeable AMPARs. Behavioral analyses found that GluR2-cKO mice were impaired on multiple hippocampus-dependent learning tasks that required NMDAR activation. This suggests that AMPAR-mediated LTP interferes with NMDAR-dependent plasticity. In contrast, NMDAR-independent learning was normal in knockout mice and required the activation of Ca(2+)-permeable AMPARs. These results suggest that GluR2-lacking AMPARs play a functional and previously unidentified role in learning; they appear to mediate changes in synaptic strength that occur after plasticity has been established by NMDARs

A Role for Calcium-Permeable AMPA Receptors in Synaptic Plasticity and Learning

A central concept in the field of learning and memory is that NMDARs are essential for synaptic plasticity and memory formation. Surprisingly then, multiple studies have found that behavioral experience can reduce or eliminate the contribution of these receptors to learning. The cellular mechanisms that mediate learning in the absence of NMDAR activation are currently unknown. To address this issue, we examined the contribution of Ca[superscript 2+]-permeable AMPARs to learning and plasticity in the hippocampus. Mutant mice were engineered with a conditional genetic deletion of GluR2 in the CA1 region of the hippocampus (GluR2-cKO mice). Electrophysiology experiments in these animals revealed a novel form of long-term potentiation (LTP) that was independent of NMDARs and mediated by GluR2-lacking Ca2+-permeable AMPARs. Behavioral analyses found that GluR2-cKO mice were impaired on multiple hippocampus-dependent learning tasks that required NMDAR activation. This suggests that AMPAR-mediated LTP interferes with NMDAR-dependent plasticity. In contrast, NMDAR-independent learning was normal in knockout mice and required the activation of Ca[superscript 2+]-permeable AMPARs. These results suggest that GluR2-lacking AMPARs play a functional and previously unidentified role in learning; they appear to mediate changes in synaptic strength that occur after plasticity has been established by NMDARs.National Health and Medical Research Council (Australia) (Grant number 188819)National Institute of Mental Health (U.S.) (grant P50-MH58880)National Science Foundation (U.S.) (grant number 0543651)National Institute of Mental Health (U.S.) (grant number MH609197)National Institute of Mental Health (U.S.) (MH62122