RT Journal Article
SR Electronic
T1 Leptin Regulates AMPA Receptor Trafficking via PTEN Inhibition
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4088
OP 4101
DO 10.1523/JNEUROSCI.3614-09.2010
VO 30
IS 11
A1 Peter R. Moult
A1 Alasdair Cross
A1 Sandra D. Santos
A1 Ana-Luisa Carvalho
A1 Yvonne Lindsay
A1 Christopher N. Connolly
A1 Andrew J. Irving
A1 Nicholas R. Leslie
A1 Jenni Harvey
YR 2010
UL http://www.jneurosci.org/content/30/11/4088.abstract
AB The hormone leptin can cross the blood–brain barrier and influences numerous brain functions (Harvey, 2007). Indeed, recent studies have demonstrated that leptin regulates activity-dependent synaptic plasticity in the CA1 region of the hippocampus (Shanley et al., 2001; Li et al., 2002; Durakoglugil et al., 2005; Moult et al., 2009). It is well documented that trafficking of AMPA receptors is pivotal for hippocampal synaptic plasticity (Collingridge et al., 2004), but there is limited knowledge of how hormonal systems like leptin influence this process. In this study we have examined how leptin influences AMPA receptor trafficking and in turn how this impacts on excitatory synaptic function. Here we show that leptin preferentially increases the cell surface expression of GluR1 and the synaptic density of GluR2-lacking AMPA receptors in adult hippocampal slices. The leptin-induced increase in surface GluR1 required NMDA receptor activation and was associated with an increase in cytoplasmic PtdIns(3,4,5)P3 levels. In addition, leptin enhanced phosphorylation of the lipid phosphatase PTEN which inhibits PTEN function and elevates PtdIns(3,4,5)P3 levels. Moreover, inhibition of PTEN mimicked and occluded the effects of leptin on GluR1 trafficking and excitatory synaptic strength. These data indicate that leptin, via a novel pathway involving PTEN inhibition, promotes GluR1 trafficking to hippocampal synapses. This process has important implications for the role of leptin in hippocampal synaptic function in health and disease.