Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 76-93 |
| Number of pages | 18 |
| Journal | Neurobiology of Aging |
| Volume | 69 |
| Early online date | 14 May 2018 |
| DOIs | |
| Publication status | Published - Sep 2018 |
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Keywords
- Leptin
- synapitc plasticity
- AMPA receptor
- Long-term depression
- NMDA receptor
- Synaptic plasticity
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Age-dependent regulation of excitatory synaptic transmission at hippocampal temporoammonic-CA1 synapses by leptin. / McGregor, Gemma; Clements, Leigh; Farah, Adham; Irving, Andrew; Harvey, Jenni (Lead / Corresponding author).
In: Neurobiology of Aging, Vol. 69, 09.2018, p. 76-93.Research output: Contribution to journal › Article
TY - JOUR
T1 - Age-dependent regulation of excitatory synaptic transmission at hippocampal temporoammonic-CA1 synapses by leptin
AU - McGregor, Gemma
AU - Clements, Leigh
AU - Farah, Adham
AU - Irving, Andrew
AU - Harvey, Jenni
N1 - 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.
PY - 2018/9
Y1 - 2018/9
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.
AB - 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.
KW - Leptin
KW - synapitc plasticity
KW - AMPA receptor
KW - Long-term depression
KW - NMDA receptor
KW - Synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=85048501942&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2018.05.007
DO - 10.1016/j.neurobiolaging.2018.05.007
M3 - Article
VL - 69
SP - 76
EP - 93
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
ER -