Fig. 6

GPER1 activation results in induction of a novel form of NMDA receptor dependent LTP at juvenile TA-CA1 synapses. Schematic representation of the cellular events contributing to the induction of a novel form of LTP induced by activation of GPER1. Treatment with the selective GPER1 agonist, G1 or endogenous E2 results in the activation of GPER1 and stimulation of ERK-dependent signalling. This leads to activation of synaptic GluN2A-containing NMDA receptors and trafficking of GluA2-lacking AMPA receptors into hippocampal TA-CA1 synapses which in turn causes a persistent increase in synaptic efficacy. In parallel, E2 is also capable of activating ERα, which also promotes synaptic insertion of GluA2-lacking AMPA receptors and an increase in TA-CA1 synaptic efficacy, via a process involving PI3K-driven signalling and activation of GluN2B-containing NMDA receptors