title: Leptin Induces a Novel Form of NMDA Receptor-Dependent LTP at Hippocampal Temporoammonic-CA1 Synapses
abstract: It is well documented that the hormone leptin regulates many central functions and that hippocampal CA1 pyramidal neurons are a key target for leptin action. Indeed, leptin modulates excitatory synaptic transmission and synaptic plasticity at the Schaffer-collateral input to CA1 neurons. However the impact of leptin on the direct temporoammonic (TA) input to CA1 neurons is not known. Here we show that leptin evokes a long-lasting increase [long-term potentiation (LTP)] in excitatory synaptic transmission at TA-CA1 synapses in rat juvenile hippocampus. Leptin-induced LTP was NMDA receptor-dependent and specifically involved the activation of GluN2B subunits. The signaling pathways underlying leptin-induced LTP involve the activation of phosphoinositide 3-kinase, but were independent of the ERK signaling cascade. Moreover, insertion of GluA2-lacking AMPA receptors was required for leptin-induced LTP as prior application of philanthotoxin prevented the effects of leptin. In addition, synaptic-induced LTP occluded the persistent increase in synaptic efficacy induced by leptin. In conclusion, these data indicate that leptin induces a novel form of NMDA receptor-dependent LTP at juvenile TA-CA1 synapses, which has important implications for the role of leptin in modulating hippocampal synaptic function in health and disease.
authors.affiliation: Division of Neuroscience, Medical Research Institute , Ninewells Hospital and Medical School , University of Dundee , Dundee DD1 9SY, United Kingdom.
authors.forename: Xiao
authors.initials: X
authors.lastname: Luo
authors.affiliation: Division of Neuroscience, Medical Research Institute , Ninewells Hospital and Medical School , University of Dundee , Dundee DD1 9SY, United Kingdom.
authors.forename: Gemma
authors.initials: G
authors.lastname: McGregor
authors.affiliation: Division of Neuroscience, Medical Research Institute , Ninewells Hospital and Medical School , University of Dundee , Dundee DD1 9SY, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Irving
authors.affiliation: Division of Neuroscience, Medical Research Institute , Ninewells Hospital and Medical School , University of Dundee , Dundee DD1 9SY, United Kingdom.
authors.forename: Jenni
authors.initials: J
authors.lastname: Harvey
keywords: NMDA receptor; excitatory synaptic transmission; leptin; synaptic plasticity