Significant advances have been made in our understanding of the hormone, leptin and its CNS actions in recent years. It is now evident that leptin has a multitude of brain functions, that extend beyond its established role in the hypothalamic control of energy balance. Additional brain regions including the hippocampus are important targets for leptin, with a high density of leptin receptors (LepRs) expressed in specific hippocampal regions and localised to CA1 synapses. Extensive evidence indicates that leptin has pro-cognitive actions, as it rapidly modifies synaptic efficacy at excitatory Schaffer collateral (SC)-CA1 and temporoammonic (TA)-CA1 synapses and enhances performance in hippocampal-dependent memory tasks. There is a functional decline in hippocampal responsiveness to leptin with age, with significant reductions in the modulatory effects of leptin at SC-CA1 and TA-CA1 synapses in aged, compared to adult hippocampus. As leptin has pro-cognitive effects, this decline in leptin sensitivity is likely to have negative consequences for cognitive function during the aging process. Here we review how evaluation of the hippocampal actions of leptin has improved our knowledge of the regulatory brain functions of leptin in health and provided significant insight into the impact of leptin in age-related neurodegenerative disorders linked to cognitive decline.

近年来，我们对激素、瘦素及其中枢神经系统作用的理解取得了重大进展。现在很明显，瘦素具有多种大脑功能，超出了其在下丘脑控制能量平衡中的既定作用。包括海马在内的其他大脑区域是瘦素的重要靶标，在特定海马区域表达高密度的瘦素受体 (LepRs)，并定位于 CA1 突触。大量证据表明，瘦素具有促认知作用，因为它可以快速改变兴奋性 Schaffer 侧支 (SC)-CA1 和颞氨 (TA)-CA1 突触的突触功效，并提高海马依赖性记忆任务的性能。随着年龄的增长，海马对瘦素的反应性功能下降，与成年海马体相比，瘦素对老年人 SC-CA1 和 TA-CA1 突触的调节作用显着降低。由于瘦素具有促认知作用，瘦素敏感性的这种下降可能会对衰老过程中的认知功能产生负面影响。在这里，我们回顾了瘦素海马作用的评估如何提高了我们对瘦素在健康中的调节性脑功能的认识，并为瘦素在与认知衰退相关的年龄相关神经退行性疾病中的影响提供了重要见解。