NMDA receptor subunit composition determines the polarity of leptin-induced synaptic plasticity. / Moult, Peter R.; Harvey, Jenni.
In: Neuropharmacology, Vol. 61, No. 5-6, 2011, p. 924-936.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - NMDA receptor subunit composition determines the polarity of leptin-induced synaptic plasticity
A1 - Moult,Peter R.
A1 - Harvey,Jenni
AU - Moult,Peter R.
AU - Harvey,Jenni
PY - 2011
Y1 - 2011
N2 - <p>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.</p>
AB - <p>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.</p>
KW - Leptin
KW - Synaptic transmission
KW - NMDA receptor
KW - Synaptic plasticity
KW - PI 3-kinase
KW - MAPK
KW - LONG-TERM POTENTIATION
KW - D-ASPARTATE RECEPTOR
KW - FUNCTIONAL-PROPERTIES
KW - HIPPOCAMPAL-NEURONS
KW - DIFFERENTIAL ROLES
KW - BRAIN-DEVELOPMENT
KW - CA1 REGION
KW - DEPRESSION
KW - RAT
KW - TRANSMISSION
U2 - 10.1016/j.neuropharm.2011.06.021
DO - 10.1016/j.neuropharm.2011.06.021
M1 - Article
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
IS - 5-6
VL - 61
SP - 924
EP - 936
ER -