G-protein coupled estrogen receptor (GPER1) activation promotes synaptic insertion of AMPA receptors and induction of chemical LTP at hippocampal temporoammonic-CA1 synapses

Molecular Brain

Research

Jenni Harvey¹  Leigh Clements¹  Amy Alexander¹  Kirsty Hamilton¹  Andrew Irving² 

[1] Division of Systems Medicine, University of Dundee, Ninewells Hospital and Medical School, DD1 9SY, Dundee, UK;Division of Systems Medicine, University of Dundee, Ninewells Hospital and Medical School, DD1 9SY, Dundee, UK;Faculty of Arts, Science and Technology, The University of Northampton, NN1 5PH, Northampton, UK;

关键词: Estrogen;    GPER1;    Synaptic transmission;    AMPA receptor;    Synaptic plasticity;    Temporoammonic;   

DOI  :  10.1186/s13041-023-01003-3

 received in 2022-09-12, accepted in 2023-01-12,  发布年份 2023

来源: Springer

【 摘 要 】

It is well documented that 17β estradiol (E2) regulates excitatory synaptic transmission at hippocampal Shaffer-collateral (SC)-CA1 synapses, via activation of the classical estrogen receptors (ERα and ERβ). Hippocampal CA1 pyramidal neurons are also innervated by the temporoammonic (TA) pathway, and excitatory TA-CA1 synapses are reported to be regulated by E2. Recent studies suggest a role for the novel G-protein coupled estrogen receptor (GPER1) at SC-CA1 synapses, however, the role of GPER1 in mediating the effects of E2 at juvenile TA-CA1 synapses is unclear. Here we demonstrate that the GPER1 agonist, G1 induces a persistent, concentration-dependent (1–10 nM) increase in excitatory synaptic transmission at TA-CA1 synapses and this effect is blocked by selective GPER1 antagonists. The ability of GPER1 to induce this novel form of chemical long-term potentiation (cLTP) was prevented following blockade of N-methyl-d-aspartate (NMDA) receptors, and it was not accompanied by any change in paired pulse facilitation ratio (PPR). GPER1-induced cLTP involved activation of ERK but was independent of phosphoinositide 3-kinase (PI3K) signalling. Prior treatment with philanthotoxin prevented the effects of G1, indicating that synaptic insertion of GluA2-lacking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors underlies GPER1-induced cLTP. Furthermore, activity-dependent LTP occluded G1‐induced cLTP and vice versa, indicating that these processes have overlapping expression mechanisms. Activity‐dependent LTP was blocked by the GPER1 antagonist, G15, suggesting that GPER1 plays a role in NMDA‐dependent LTP at juvenile TA‐CA1 synapses. These findings add a new dimension to our understanding of GPER1 in modulating neuronal plasticity with relevance to age-related neurodegenerative conditions.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

41116_2022_35_Article_IEq514.gif

Fig. 28

41116_2022_35_Article_IEq495.gif

41116_2022_35_Article_IEq478.gif

41116_2022_35_Article_IEq470.gif

Fig. 12