Intrinsic membrane properties and cholinergic modulation of mouse basal forebrain glutamatergic neurons in vitro.
Intrinsic membrane properties and cholinergic modulation of mouse basal forebrain glutamatergic neurons in vitro.
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体外小鼠基底前脑谷氨酸能神经元的内在膜特性和胆碱能调节。
DOI：
10.1016/j.neuroscience.2017.04.002
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发表时间：
2017
期刊：
影响因子：
3.3
通讯作者：
Brown,RitchieE
中科院分区：
文献类型：
--
作者：
Yang,Chun;McKenna,JamesT;Brown,RitchieE
基底前脑（BF）控制睡眠-觉醒周期，注意力和奖励处理。与胆碱能神经元和GABA能神经元相比，BF能神经元由于难以识别而知之甚少。在这里，我们使用囊泡谷氨酸转运蛋白2（vGluT 2）-tdTomato小鼠，表达一个红色荧光蛋白（tdTomato）的BF谷氨酸能神经元（vGluT 2+）的主要群体，以表征其内在的电特性和胆碱能调制。从冠状BF切片中的vGluT 2+神经元进行全细胞膜片钳记录。大多数BF vGluT 2+神经元为小型/中型（<20 µm），表现出中等大小的H电流，最大放电频率为250 Hz。然而，背侧BF（腹侧苍白球）的vGluT 2+神经元有更大的H-电流和更高的最大放电频率（83 Hz）。BF vGluT 2+神经元的一个子集表现出爆发/簇放电。大多数vGluT 2+神经元具有低阈值钙峰/电流。vGluT 2+神经元位于腹内侧区的BF（在或邻近的水平肢体的对角线带）强烈超极化的胆碱能激动剂，卡巴胆碱，这一发现显然与他们的放电增加在清醒/REM睡眠和假设的作用，在唤醒促进冲突。相反，大多数vGluT 2+神经元位于外侧BF（大细胞视前区）或背侧BF没有响应卡巴胆碱。我们的研究结果表明，BF胆碱能神经元是异质性的，并具有形态学，电学和药理学特性，使其区别于BF胆碱能和GABA能神经元。vGluT 2+神经元的一个子集，可能是那些投射到奖励相关区域（如缰）的神经元，被胆碱能输入超极化，这可能导致奖励相关事件期间的阶段性抑制。
The basal forebrain (BF) controls sleep–wake cycles, attention and reward processing. Compared to cholinergic and GABAergic neurons, BF glutamatergic neurons are less well understood, due to difficulties in identification. Here, we use vesicular glutamate transporter 2 (vGluT2)-tdTomato mice, expressing a red fluorescent protein (tdTomato) in the major group of BF glutamatergic neurons (vGluT2+) to characterize their intrinsic electrical properties and cholinergic modulation. Whole-cell, patch-clamp recordings were made from vGluT2+ neurons in coronal BF slices. Most BF vGluT2+ neurons were small/medium sized (<20 µm), exhibited moderately sized H-currents and had a maximal firing frequency of ∼50 Hz. However, vGluT2+ neurons in dorsal BF (ventral pallidum) had larger H-currents and a higher maximal firing rate (83 Hz). A subset of BF vGluT2+ neurons exhibited burst/cluster firing. Most vGluT2+ neurons had low-threshold calcium spikes/currents. vGluT2+ neurons located in ventromedial regions of BF (in or adjacent to the horizontal limb of the diagonal band) were strongly hyperpolarized by the cholinergic agonist, carbachol, a finding apparently in conflict with their increased discharge during wakefulness/REM sleep and hypothesized role in wake-promotion. In contrast, most vGluT2+ neurons located in lateral BF (magnocellular preoptic area) or dorsal BF did not respond to carbachol. Our results suggest that BF glutamatergic neurons are heterogeneous and have morphological, electrical and pharmacological properties which distinguish them from BF cholinergic and GABAergic neurons. A subset of vGluT2+ neurons, possibly those neurons which project to reward-related areas such as the habenula, are hyperpolarized by cholinergic inputs, which may cause phasic inhibition during reward-related events.