Activation of estrogen receptor α induces a novel form of long-term potentiation at hippocampal temporoammonic-CA1 synapses

Leigh Clements, Jenni Harvey (Lead / Corresponding author)

Research output: Contribution to journalArticle

Abstract

Background: 17β estradiol (E2) rapidly regulates excitatory synaptic transmission at the classical Schaffer collateral (SC) input to hippocampal CA1 neurons. However, the impact of E2 on excitatory synaptic transmission at the distinct temporoammonic (TA) input to CA1 neurons, and the estrogen receptors involved, are less clear.

Experimental Approach
: Extracellular recordings were used to monitor excitatory synaptic transmission in hippocampal slices from juvenile male (P11-24) Sprague Dawley rats. Immunocytochemistry combined with confocal microscopy was used to monitor the surface expression of the AMPA receptor (AMPAR) subunit, GluA1 in hippocampal neurons cultured from neonatal (P0-3) rats.

Results: Here we show that E2 induces a novel form of LTP at TA-CA1 synapses; an effect mirrored by the ERα agonist, PPT and blocked by an ERα antagonist. ERα-induced LTP is NMDA receptor (NMDAR)-dependent and involves a postsynaptic expression mechanism that requires PI 3-kinase signalling and synaptic insertion of GluA2-lacking AMPA receptors. ERα-induced LTP has overlapping expression mechanisms with classical Hebbian LTP, as HFS-induced LTP occluded PPT-induced LTP and vice versa. In addition, activity-dependent LTP was blocked by the ERα antagonist, suggesting that ERα activation is involved in NMDA-LTP at TA-CA1 synapses.

Conclusions: ERα induces a novel form of long-term potentiation at juvenile male hippocampal TA-CA1 synapses. As TA-CA1 synapses are implicated in episodic memory processes, and are an early target for neurodegeneration, these findings have important implications for the role of estrogens in CNS health and neurodegenerative disease.
Original languageEnglish
JournalBritish Journal of Pharmacology
Early online date22 Oct 2019
DOIs
Publication statusE-pub ahead of print - 22 Oct 2019

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Long-Term Potentiation
Estrogen Receptors
Synapses
Synaptic Transmission
AMPA Receptors
Neurons
Episodic Memory
Central Nervous System Diseases
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Phosphatidylinositol 3-Kinases
Confocal Microscopy
Neurodegenerative Diseases
Sprague Dawley Rats
Estradiol
Hippocampus
Estrogens
Immunohistochemistry
Health

Keywords

  • ERα
  • synaptic plasticity
  • temporoammonic
  • AMPA receptor trafficking
  • estrogen

Cite this

@article{fcfb039c67804ddcaa43b6a3c89e8923,
title = "Activation of estrogen receptor α induces a novel form of long-term potentiation at hippocampal temporoammonic-CA1 synapses",
abstract = "Background: 17β estradiol (E2) rapidly regulates excitatory synaptic transmission at the classical Schaffer collateral (SC) input to hippocampal CA1 neurons. However, the impact of E2 on excitatory synaptic transmission at the distinct temporoammonic (TA) input to CA1 neurons, and the estrogen receptors involved, are less clear.Experimental Approach: Extracellular recordings were used to monitor excitatory synaptic transmission in hippocampal slices from juvenile male (P11-24) Sprague Dawley rats. Immunocytochemistry combined with confocal microscopy was used to monitor the surface expression of the AMPA receptor (AMPAR) subunit, GluA1 in hippocampal neurons cultured from neonatal (P0-3) rats. Results: Here we show that E2 induces a novel form of LTP at TA-CA1 synapses; an effect mirrored by the ERα agonist, PPT and blocked by an ERα antagonist. ERα-induced LTP is NMDA receptor (NMDAR)-dependent and involves a postsynaptic expression mechanism that requires PI 3-kinase signalling and synaptic insertion of GluA2-lacking AMPA receptors. ERα-induced LTP has overlapping expression mechanisms with classical Hebbian LTP, as HFS-induced LTP occluded PPT-induced LTP and vice versa. In addition, activity-dependent LTP was blocked by the ERα antagonist, suggesting that ERα activation is involved in NMDA-LTP at TA-CA1 synapses. Conclusions: ERα induces a novel form of long-term potentiation at juvenile male hippocampal TA-CA1 synapses. As TA-CA1 synapses are implicated in episodic memory processes, and are an early target for neurodegeneration, these findings have important implications for the role of estrogens in CNS health and neurodegenerative disease.",
keywords = "ERα, synaptic plasticity, temporoammonic, AMPA receptor trafficking, estrogen",
author = "Leigh Clements and Jenni Harvey",
note = "This article is protected by copyright. All rights reserved.",
year = "2019",
month = "10",
day = "22",
doi = "10.1111/bph.14880",
language = "English",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley",

}

TY - JOUR

T1 - Activation of estrogen receptor α induces a novel form of long-term potentiation at hippocampal temporoammonic-CA1 synapses

AU - Clements, Leigh

AU - Harvey, Jenni

N1 - This article is protected by copyright. All rights reserved.

PY - 2019/10/22

Y1 - 2019/10/22

N2 - Background: 17β estradiol (E2) rapidly regulates excitatory synaptic transmission at the classical Schaffer collateral (SC) input to hippocampal CA1 neurons. However, the impact of E2 on excitatory synaptic transmission at the distinct temporoammonic (TA) input to CA1 neurons, and the estrogen receptors involved, are less clear.Experimental Approach: Extracellular recordings were used to monitor excitatory synaptic transmission in hippocampal slices from juvenile male (P11-24) Sprague Dawley rats. Immunocytochemistry combined with confocal microscopy was used to monitor the surface expression of the AMPA receptor (AMPAR) subunit, GluA1 in hippocampal neurons cultured from neonatal (P0-3) rats. Results: Here we show that E2 induces a novel form of LTP at TA-CA1 synapses; an effect mirrored by the ERα agonist, PPT and blocked by an ERα antagonist. ERα-induced LTP is NMDA receptor (NMDAR)-dependent and involves a postsynaptic expression mechanism that requires PI 3-kinase signalling and synaptic insertion of GluA2-lacking AMPA receptors. ERα-induced LTP has overlapping expression mechanisms with classical Hebbian LTP, as HFS-induced LTP occluded PPT-induced LTP and vice versa. In addition, activity-dependent LTP was blocked by the ERα antagonist, suggesting that ERα activation is involved in NMDA-LTP at TA-CA1 synapses. Conclusions: ERα induces a novel form of long-term potentiation at juvenile male hippocampal TA-CA1 synapses. As TA-CA1 synapses are implicated in episodic memory processes, and are an early target for neurodegeneration, these findings have important implications for the role of estrogens in CNS health and neurodegenerative disease.

AB - Background: 17β estradiol (E2) rapidly regulates excitatory synaptic transmission at the classical Schaffer collateral (SC) input to hippocampal CA1 neurons. However, the impact of E2 on excitatory synaptic transmission at the distinct temporoammonic (TA) input to CA1 neurons, and the estrogen receptors involved, are less clear.Experimental Approach: Extracellular recordings were used to monitor excitatory synaptic transmission in hippocampal slices from juvenile male (P11-24) Sprague Dawley rats. Immunocytochemistry combined with confocal microscopy was used to monitor the surface expression of the AMPA receptor (AMPAR) subunit, GluA1 in hippocampal neurons cultured from neonatal (P0-3) rats. Results: Here we show that E2 induces a novel form of LTP at TA-CA1 synapses; an effect mirrored by the ERα agonist, PPT and blocked by an ERα antagonist. ERα-induced LTP is NMDA receptor (NMDAR)-dependent and involves a postsynaptic expression mechanism that requires PI 3-kinase signalling and synaptic insertion of GluA2-lacking AMPA receptors. ERα-induced LTP has overlapping expression mechanisms with classical Hebbian LTP, as HFS-induced LTP occluded PPT-induced LTP and vice versa. In addition, activity-dependent LTP was blocked by the ERα antagonist, suggesting that ERα activation is involved in NMDA-LTP at TA-CA1 synapses. Conclusions: ERα induces a novel form of long-term potentiation at juvenile male hippocampal TA-CA1 synapses. As TA-CA1 synapses are implicated in episodic memory processes, and are an early target for neurodegeneration, these findings have important implications for the role of estrogens in CNS health and neurodegenerative disease.

KW - ERα

KW - synaptic plasticity

KW - temporoammonic

KW - AMPA receptor trafficking

KW - estrogen

U2 - 10.1111/bph.14880

DO - 10.1111/bph.14880

M3 - Article

C2 - 31637699

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

ER -