A metabolic function of the hippocampal sharp wave-ripple

The hippocampus has previously been implicated in both cognitive and endocrine functions. We simultaneously measured electrophysiological activity from the hippocampus and interstitial glucose concentrations in the body of freely behaving rats to identify an activity pattern that may link these disparate functions of the hippocampus. Here we report that clusters of sharp wave-ripples recorded from the hippocampus reliably predicted a decrease in peripheral glucose concentrations within about 10 min. This correlation was not dependent on circadian, ultradian or meal-triggered fluctuations, could be mimicked with optogenetically induced ripples in the hippocampus (but not in the parietal cortex) and was attenuated to chance levels by pharmacogenetically suppressing activity of the lateral septum, which is the major conduit between the hippocampus and the hypothalamus. Our findings demonstrate that a function of the sharp wave-ripple is to modulate peripheral glucose homeostasis, and offer a mechanism for the link between sleep disruption and blood glucose dysregulation in type 2 diabetes.

此前已有研究表明，海马体（hippocampus）同时参与认知与内分泌功能。本研究同步记录了自由活动大鼠的海马体电生理活动与体内组织间液葡萄糖浓度，以探寻可能关联海马体这两类迥异功能的活动模式。本文报道：从海马体记录到的尖波涟漪（sharp wave-ripples）集群可稳定预测约10分钟内外周葡萄糖浓度的下降。该相关性不受昼夜节律、超昼夜节律或进餐触发波动的影响；用光遗传手段诱导海马体（而非顶叶皮层（parietal cortex））产生的尖波涟漪可复刻这一现象，而通过药物遗传学抑制作为海马体与下丘脑（hypothalamus）间主要传导通路的外侧隔核（lateral septum）活动，则会使该相关性减弱至随机水平。本研究结果证实，尖波涟漪的一项功能是调节外周葡萄糖稳态，并为睡眠中断与2型糖尿病患者血糖失调之间的关联提供了潜在机制。