TY - JOUR T1 - Leptin induces a novel form of NMDA receptor-dependent LTP at hippocampal temporoammonic-CA1 synapses JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0007-15.2015 SP - ENEURO.0007-15.2015 AU - Xiao Luo AU - Gemma McGregor AU - Andrew J Irving AU - Jenni Harvey Y1 - 2015/05/26 UR - http://www.eneuro.org/content/early/2015/05/27/ENEURO.0007-15.2015.abstract N2 - 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 (SC) 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 (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 signalling pathways underlying leptin-induced LTP involve the activation of PI 3-kinase, but were independent of the ERK signalling 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.Significance Statement: Hippocampal CA1 pyramidal neurons receive two anatomically distinct glutamatergic inputs that have distinct roles in learning and memory. The hormone leptin markedly influences excitatory synaptic transmission at the indirect Schaffer-collateral (SC) pathway to CA1 neurons. However the impact of leptin on the anatomically distinct temporoammonic (TA) input to CA1 pyramidal neurons is unknown. Here we provide the first compelling evidence that leptin induces a novel form of NMDA receptor-dependent long term potentiation (LTP) at TA-CA1 synapses that shares similar expression mechanisms to activity dependent LTP at this synapse. As the direct TA pathway is required for memory consolidation and place cell firing, these findings have important implications for leptin’s role in regulating spatial information and long term memory consolidation. ER -