Acetylcholine modulates gamma frequency oscillations in the hippocampus by activation of muscarinic M1 receptors.
Acetylcholine modulates gamma frequency oscillations in the hippocampus by activation of muscarinic M1 receptors.
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DOI：
10.1111/ejn.13582
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Mellor JR
中科院分区：
文献类型：
--
作者：
Betterton RT;Broad LM;Tsaneva-Atanasova K;Mellor JR
伽马振荡的调制对于信息处理很重要，而伽马振荡的中断是精神分裂症和阿尔茨海默病的一个显著特征。伽玛振荡是由兴奋性神经元和抑制性神经元相互作用产生的，其精确的频率和幅度由兴奋和抑制的平衡控制。乙酰胆碱增强锥体神经元的内在兴奋性，抑制兴奋性和抑制性突触传递，但对伽马振荡的净调制作用尚不清楚。在这里，我们发现，低浓度的广谱胆碱能激动剂卡巴胆碱可以增强小鼠海马片CA3区光遗传诱导的伽马振荡的功率，但不是频率，但在高浓度时会降低。这种伽马振荡的双向调制是通过神经元去极化在数学模型中复制的，但不是通过减少突触电导来模仿毒鼠强M1受体激活的效果。M1受体的预测作用得到了实验的支持；选择性M1受体激动剂复制了乙酰胆碱对伽马振荡的双向调节，并通过M1受体的遗传缺失来阻止。这些结果表明，海马区CA3区释放的乙酰胆碱主要通过M_1受体调节伽玛振荡功率，而不是以双向和剂量依赖的方式调节频率。
Modulation of gamma oscillations is important for the processing of information and the disruption of gamma oscillations is a prominent feature of schizophrenia and Alzheimer's disease. Gamma oscillations are generated by the interaction of excitatory and inhibitory neurons where their precise frequency and amplitude are controlled by the balance of excitation and inhibition. Acetylcholine enhances the intrinsic excitability of pyramidal neurons and suppresses both excitatory and inhibitory synaptic transmission, but the net modulatory effect on gamma oscillations is not known. Here, we find that the power, but not frequency, of optogenetically induced gamma oscillations in the CA3 region of mouse hippocampal slices is enhanced by low concentrations of the broad‐spectrum cholinergic agonist carbachol but reduced at higher concentrations. This bidirectional modulation of gamma oscillations is replicated within a mathematical model by neuronal depolarisation, but not by reducing synaptic conductances, mimicking the effects of muscarinic M1 receptor activation. The predicted role for M1 receptors was supported experimentally; bidirectional modulation of gamma oscillations by acetylcholine was replicated by a selective M1 receptor agonist and prevented by genetic deletion of M1 receptors. These results reveal that acetylcholine release in CA3 of the hippocampus modulates gamma oscillation power but not frequency in a bidirectional and dose‐dependent manner by acting primarily through muscarinic M1 receptors.
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影响因子：
13.9
作者：
Buzsáki G;Wang XJ
通讯作者：
Wang XJ
DOI：
10.1523/jneurosci.0337-12.2012
发表时间：
2012-06-20
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Digby GJ;Noetzel MJ;Bubser M;Utley TJ;Walker AG;Byun NE;Lebois EP;Xiang Z;Sheffler DJ;Cho HP;Davis AA;Nemirovsky NE;Mennenga SE;Camp BW;Bimonte-Nelson HA;Bode J;Italiano K;Morrison R;Daniels JS;Niswender CM;Olive MF;Lindsley CW;Jones CK;Conn PJ
通讯作者：
Conn PJ
DOI：
10.1073/pnas.0609440103
发表时间：
2006-12-26
影响因子：
11.1
作者：
Cho, R. Y.;Konecky, R. O.;Carter, C. S.
通讯作者：
Carter, C. S.
DOI：
10.1093/cercor/bhv227
发表时间：
2016-01
期刊：
Cerebral cortex (New York, N.Y. : 1991)
影响因子：
--
作者：
Dennis SH;Pasqui F;Colvin EM;Sanger H;Mogg AJ;Felder CC;Broad LM;Fitzjohn SM;Isaac JT;Mellor JR
通讯作者：
Mellor JR
影响因子：
25
作者：
Akam, Thomas;Oren, Iris;Kullmann, Dimitri M.
通讯作者：
Kullmann, Dimitri M.