| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Clements, Leigh Alexander, Amy Hamilton, Kirsty Irving, Andrew Harvey, Jenni |
| Abstract | 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. |
| Related Links | https://molecularbrain.biomedcentral.com/counter/pdf/10.1186/s13041-023-01003-3.pdf |
| Ending Page | 18 |
| Page Count | 18 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17566606 |
| DOI | 10.1186/s13041-023-01003-3 |
| Journal | Molecular Brain |
| Issue Number | 1 |
| Volume Number | 16 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2023-01-28 |
| Access Restriction | Open |
| Subject Keyword | Neurosciences Neurology Psychopharmacology Estrogen GPER1 Synaptic transmission AMPA receptor Synaptic plasticity Temporoammonic |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cellular and Molecular Neuroscience Molecular Biology |
| Journal Impact Factor | 3.3/2023 |
| 5-Year Journal Impact Factor | 3.8/2023 |
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