Institute of Physiology and Pathophysiology, Heidelberg University, Heidelberg, Germany.
J Neurochem. 2014 Jun;129(5):792-805. doi: 10.1111/jnc.12693. Epub 2014 Mar 19.
The cholinergic system is critically involved in the modulation of cognitive functions, including learning and memory. Acetylcholine acts through muscarinic (mAChRs) and nicotinic receptors (nAChRs), which are both abundantly expressed in the hippocampus. Previous evidence indicates that choline, the precursor and degradation product of Acetylcholine, can itself activate nAChRs and thereby affects intrinsic and synaptic neuronal functions. Here, we asked whether the cellular actions of choline directly affect hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R) and can induce gamma oscillations. In addition, choline reduces synaptic transmission between hippocampal subfields CA3 and CA1. Surprisingly, these effects are mediated by activation of both mAChRs and α7-containing nAChRs. Most nicotinic effects became only apparent after local, fast application of choline, indicating rapid desensitization kinetics of nAChRs. Effects were still present following block of choline uptake and are, therefore, likely because of direct actions of choline at the respective receptors. Together, choline turns out to be a potent regulator of patterned network activity within the hippocampus. These actions may be of importance for understanding state transitions in normal and pathologically altered neuronal networks. In this study we asked whether choline, the precursor and degradation product of acetylcholine, directly affects hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R). In addition, choline reduces synaptic transmission between hippocampal subfields. These effects are mediated by direct activation of muscarinic as well as nicotinic cholinergic pathways. Together, choline turns out to be a potent regulator of patterned activity within hippocampal networks.
胆碱能系统在调节认知功能（包括学习和记忆）方面起着至关重要的作用。乙酰胆碱通过毒蕈碱型（mAChR）和烟碱型（nAChR）受体发挥作用，这两种受体在海马体中均大量表达。先前的证据表明，作为乙酰胆碱前体和降解产物的胆碱本身可以激活 nAChR，从而影响内在和突触神经元功能。在这里，我们想知道胆碱的细胞作用是否直接影响海马体网络活动。使用小鼠海马切片，我们发现胆碱能有效抑制自发出现的尖波-涟漪复合波（SPW-R），并能诱导γ振荡。此外，胆碱能减少海马体 CA3 和 CA1 亚区之间的突触传递。令人惊讶的是，这些效应是通过激活 mAChR 和包含α7 的 nAChR 介导的。大多数烟碱效应只有在胆碱快速局部应用后才变得明显，这表明 nAChR 的快速脱敏动力学。在阻断胆碱摄取后，这些效应仍然存在，因此很可能是由于胆碱在相应受体上的直接作用。总之，胆碱是海马体中模式网络活动的一种有效调节剂。这些作用对于理解正常和病理性改变的神经元网络中的状态转换可能很重要。在这项研究中，我们想知道乙酰胆碱的前体和降解产物胆碱是否直接影响海马体的网络活动。使用小鼠海马切片，我们发现胆碱能有效抑制自发出现的尖波-涟漪复合波（SPW-R）。此外，胆碱能减少海马体亚区之间的突触传递。这些效应是通过直接激活毒蕈碱型和烟碱型胆碱能途径介导的。总之，胆碱是海马体网络中模式活动的一种有效调节剂。
