Orexin Receptor Activation Generates Gamma Band Input to Cholinergic and Serotonergic Arousal System Neurons and Drives an Intrinsic Ca(2+)-Dependent Resonance in LDT and PPT Cholinergic Neurons.
Orexin Receptor Activation Generates Gamma Band Input to Cholinergic and Serotonergic Arousal System Neurons and Drives an Intrinsic Ca(2+)-Dependent Resonance in LDT and PPT Cholinergic Neurons.
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DOI：
10.3389/fneur.2015.00120
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发表时间：
2015
影响因子：
3.4
通讯作者：
Leonard CS
中科院分区：
文献类型：
--
作者：
Ishibashi M;Gumenchuk I;Kang B;Steger C;Lynn E;Molina NE;Eisenberg LM;Leonard CS
清醒状态的一个标志是脑电能量向更高频率转移，皮质内伽马活动同步(30-60赫兹)--这是一个与高级认知功能相关的过程。包括胆碱能外侧背核(LDT)、桥脚(PPT)被盖神经元和5-羟色胺能中缝背核(DR)神经元在内的上行觉醒系统促进这种状态。最近，这个系统被提出作为伽马波发生器，部分原因是一些神经元在伽马频率上产生高阈值的、依赖于钙离子的振荡。然而，目前还不知道这些神经元的觉醒相关输入是否会产生这种振荡，或者这种振荡是否会传递到神经元靶点。由于关键的觉醒输入来自下丘脑增食欲素(下丘脑)神经元，我们研究了异常嘈杂的去极化增食欲素电流是否可以为胆碱能和5-羟色胺能神经元提供显著的伽马输入，以及这种输入是否可以驱动钙依赖的振荡。表达CRE诱导的胆碱能LDT和PPT以及5-羟色胺能DR神经元荧光的小鼠脑片获得全细胞记录。在首次量化了报告在胆碱能和5-羟色胺能神经元中的表达准确性后，我们发现食欲素电流产生了显著的高频，包括伽马，输入到胆碱能和5-羟色胺能神经元。然后，通过使用动态钳位，我们发现在胆碱能神经元上增加噪声的增食欲素电导诱导了一种钙依赖的共振，该共振在theta和α频率范围(4-14赫兹)达到峰值，并延伸到100赫兹。我们认为，这种食欲素电流噪声和钙离子依赖的共振协同作用，促进高频突触输入到动作电位的编码，并帮助确保胆碱能神经元在脑电激活过程中放电。这种活动可以加强丘脑皮质状态，支持觉醒、快速眼动睡眠和皮质内伽马。
A hallmark of the waking state is a shift in EEG power to higher frequencies with epochs of synchronized intracortical gamma activity (30–60 Hz) – a process associated with high-level cognitive functions. The ascending arousal system, including cholinergic laterodorsal (LDT) and pedunculopontine (PPT) tegmental neurons and serotonergic dorsal raphe (DR) neurons, promotes this state. Recently, this system has been proposed as a gamma wave generator, in part, because some neurons produce high-threshold, Ca2+-dependent oscillations at gamma frequencies. However, it is not known whether arousal-related inputs to these neurons generate such oscillations, or whether such oscillations are ever transmitted to neuronal targets. Since key arousal input arises from hypothalamic orexin (hypocretin) neurons, we investigated whether the unusually noisy, depolarizing orexin current could provide significant gamma input to cholinergic and serotonergic neurons, and whether such input could drive Ca2+-dependent oscillations. Whole-cell recordings in brain slices were obtained from mice expressing Cre-induced fluorescence in cholinergic LDT and PPT, and serotonergic DR neurons. After first quantifying reporter expression accuracy in cholinergic and serotonergic neurons, we found that the orexin current produced significant high frequency, including gamma, input to both cholinergic and serotonergic neurons. Then, by using a dynamic clamp, we found that adding a noisy orexin conductance to cholinergic neurons induced a Ca2+-dependent resonance that peaked in the theta and alpha frequency range (4–14 Hz) and extended up to 100 Hz. We propose that this orexin current noise and the Ca2+ dependent resonance work synergistically to boost the encoding of high-frequency synaptic inputs into action potentials and to help ensure cholinergic neurons fire during EEG activation. This activity could reinforce thalamocortical states supporting arousal, REM sleep, and intracortical gamma.
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影响因子：
4.3
作者：
Kohlmeier KA;Tyler CJ;Kalogiannis M;Ishibashi M;Kristensen MP;Gumenchuk I;Chemelli RM;Kisanuki YY;Yanagisawa M;Leonard CS
通讯作者：
Leonard CS
影响因子：
13.9
作者：
Buzsáki G;Wang XJ
通讯作者：
Wang XJ
影响因子：
5.3
作者：
Higgs, Matthew H.;Slee, Sean J.;Spain, William J.
通讯作者：
Spain, William J.
影响因子：
5.3
作者：
Lee, MG;Hassani, OK;Jones, BE
通讯作者：
Jones, BE
影响因子：
5.3
作者：
Boucetta, Soufiane;Cisse, Youssouf;Jones, Barbara E.
通讯作者：
Jones, Barbara E.