Figure 2.

Schematic of common signalling pathways underlying activity-dependent and leptin-dependent synaptic plasticity. During LTP, activation of NMDA receptors stimulates PI 3-kinase and subsequent inhibition of GSK3β at hippocampal CA1 synapses. Activation of this pathway promotes delivery of AMPA receptors to synapses which in turn results in a persistent increase in the efficacy of excitatory synaptic transmission (LTP). In a similar manner, following leptin binding to leptin receptors, the activity of PI 3-kinase is increased resulting in AMPA receptor exocytosis and a sustained increased in synaptic efficacy (leptin-induced LTP). Although neuronal leptin receptors are capable of inhibiting GSK3β, via PI 3-kinase, it is unclear if GSK3β plays a role in leptin-induced LTP. During LTD, stimulation of NMDA receptors activates PP1 leading to increased GSK3β activity and subsequent AMPA receptor endocytosis and LTD. Activation of the JAK2-STAT3 pathway has also recently been implicated in NMDA receptor-dependent LTD. Although the JAK2-STAT3 pathway is a key downstream target of neuronal leptin receptors, it is not known if this pathway plays a role in leptin-dependent synaptic plasticity. (Online version in colour.)