Age-dependent regulation of excitatory synaptic transmission at hippocampal temporoammonic-CA1 synapses by leptin

Gemma McGregor, Leigh Clements, Adham Farah, Andrew Irving, Jenni Harvey (Lead / Corresponding author)

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Abstract

The hippocampus is a key target for the hormone leptin and leptin regulation of excitatory synaptic transmission at Schaffer-collateral (SC)-CA1 synapses during ageing are well documented. However, little is known about the age-dependent actions of leptin at the temporoammonic (TA) input to CA1 neurons. Here we show that leptin induces a novel form of NMDA receptor-dependent long term depression (LTD) at adult (12-24 week old) TACA1 synapses. Leptin-induced LTD requires activation of canonical JAK2-STAT3 signalling and removal of GluA1-containing AMPA receptors from synapses. Moreover, leptin-induced LTD is occluded by activity-dependent LTD at TA-CA1 synapses. In contrast, leptin has no effect on excitatory synaptic transmission at aged (12-14 month old) TA-CA1 synapses and low frequency stimulation (LFS) also fails to induce LTD at this age. These findings demonstrate clear age-related alterations in the leptin sensitivity of TA-CA1 synapses and provide valuable information on how the leptin system alters with age. As leptin has been linked to Alzheimer’s disease (AD), these findings have important implications for understanding of age-related disorders like AD.
Original languageEnglish
Pages (from-to)76-93
Number of pages18
JournalNeurobiology of Aging
Volume69
Early online date14 May 2018
DOIs
Publication statusPublished - Sep 2018

Fingerprint

Leptin
Synaptic Transmission
Synapses
Depression
Hippocampus
Alzheimer Disease
AMPA Receptors
N-Methyl-D-Aspartate Receptors
Hormones
Neurons

Keywords

  • Leptin
  • synapitc plasticity
  • AMPA receptor
  • Long-term depression
  • NMDA receptor
  • Synaptic plasticity

Cite this

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title = "Age-dependent regulation of excitatory synaptic transmission at hippocampal temporoammonic-CA1 synapses by leptin",
abstract = "The hippocampus is a key target for the hormone leptin and leptin regulation of excitatory synaptic transmission at Schaffer-collateral (SC)-CA1 synapses during ageing are well documented. However, little is known about the age-dependent actions of leptin at the temporoammonic (TA) input to CA1 neurons. Here we show that leptin induces a novel form of NMDA receptor-dependent long term depression (LTD) at adult (12-24 week old) TACA1 synapses. Leptin-induced LTD requires activation of canonical JAK2-STAT3 signalling and removal of GluA1-containing AMPA receptors from synapses. Moreover, leptin-induced LTD is occluded by activity-dependent LTD at TA-CA1 synapses. In contrast, leptin has no effect on excitatory synaptic transmission at aged (12-14 month old) TA-CA1 synapses and low frequency stimulation (LFS) also fails to induce LTD at this age. These findings demonstrate clear age-related alterations in the leptin sensitivity of TA-CA1 synapses and provide valuable information on how the leptin system alters with age. As leptin has been linked to Alzheimer’s disease (AD), these findings have important implications for understanding of age-related disorders like AD.",
keywords = "Leptin, synapitc plasticity, AMPA receptor, Long-term depression, NMDA receptor, Synaptic plasticity",
author = "Gemma McGregor and Leigh Clements and Adham Farah and Andrew Irving and Jenni Harvey",
note = "J.H. is funded by The Anonymous Trust and Tenovus. GM is supported by a BBSRC Eastbio studentship. The authors would also like to thank Karen-Anne Bollan for her technical assistance with the surface biotinylation assay and the members of Dr Will Fuller’s laboratory for use of the Bio-Rad ChemiDoc XRS imaging system and their technical help.",
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AU - Clements, Leigh

AU - Farah, Adham

AU - Irving, Andrew

AU - Harvey, Jenni

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N2 - The hippocampus is a key target for the hormone leptin and leptin regulation of excitatory synaptic transmission at Schaffer-collateral (SC)-CA1 synapses during ageing are well documented. However, little is known about the age-dependent actions of leptin at the temporoammonic (TA) input to CA1 neurons. Here we show that leptin induces a novel form of NMDA receptor-dependent long term depression (LTD) at adult (12-24 week old) TACA1 synapses. Leptin-induced LTD requires activation of canonical JAK2-STAT3 signalling and removal of GluA1-containing AMPA receptors from synapses. Moreover, leptin-induced LTD is occluded by activity-dependent LTD at TA-CA1 synapses. In contrast, leptin has no effect on excitatory synaptic transmission at aged (12-14 month old) TA-CA1 synapses and low frequency stimulation (LFS) also fails to induce LTD at this age. These findings demonstrate clear age-related alterations in the leptin sensitivity of TA-CA1 synapses and provide valuable information on how the leptin system alters with age. As leptin has been linked to Alzheimer’s disease (AD), these findings have important implications for understanding of age-related disorders like AD.

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