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NMDA receptor subunit composition determines the polarity of leptin-induced synaptic plasticity

NMDA receptor subunit composition determines the polarity of leptin-induced synaptic plasticity

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  • Peter R. Moult
  • Jenni Harvey (Lead / Corresponding author)

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Original languageEnglish
Pages (from-to)924-936
Number of pages13
Issue number5-6
StatePublished - 2011


Leptin is a hormone that crosses the blood-brain barrier and regulates numerous CNS functions. The hippocampus in particular is an important site for leptin action. Indeed, leptin markedly influences excitatory synaptic transmission and synaptic plasticity in this brain region. Recent studies indicate that leptin modulation of hippocampal excitatory synaptic transmission is age-dependent however the cellular basis for this is unclear. Here we show that early in development leptin evokes a transient (P11-18) or persistent (P5-8) depression of synaptic transmission, whereas leptin evokes a long lasting increase (LIP) in synaptic strength in adulthood. The synaptic depressions induced by leptin required activation of NMDA receptor GluN2B subunits and the ERK signalling cascade. Conversely, leptin-induced LIP in adult was mediated by GluN2A subunits and involved PI 3-kinase dependent signalling. In addition, low-frequency stimulus (LFS)-evoked LTD occluded the persistent effects of leptin at P5-8 and vice versa. Similarly, synaptically-induced LIP occluded the persistent increase in synaptic transmission induced by leptin, indicating that similar expression mechanisms underlie leptin-induced LTD and LFS-induced LTD at P5-8, and leptin-induced LIP and HFS-induced LIP in adult. These findings have important implications for the role of leptin in hippocampal synaptic function during early neuronal development and in aging. (C) 2011 Elsevier Ltd. All rights reserved.



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