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

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.