Cholinergic responses and intrinsic membrane properties of developing thalamic parafascicular neurons.
Cholinergic responses and intrinsic membrane properties of developing thalamic parafascicular neurons.
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DOI：
10.1152/jn.91132.2008
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发表时间：
2009-08
影响因子：
2.5
通讯作者：
Meijun Ye;A. Hayar;E. Garcia-Rill
中科院分区：
文献类型：
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作者：
Meijun Ye;A. Hayar;E. Garcia-Rill
束旁核(Pf)神经元接受来自桥脑脚核(PPN)的胆碱能输入，该核在清醒和快速眼动睡眠时是活跃的。从出生到青春期，人类的REM睡眠呈发育性减少，大鼠的REM睡眠有10-30天的发育减少。以前的研究已经证实，在REM睡眠发育性下降的过程中，PPN中毒碱能和5-HT1受体介导的抑制增加，并从兴奋性GABA(A)反应转变为抑制性GABA(A)反应。然而，在发育过程中，PF细胞对来自PPN的胆碱能输入的反应还没有进行过研究，PPN是上升胆碱能投射的主要靶点，可能是皮层产生节律性振荡的重要机制。用全细胞膜片钳记录9~20天龄大鼠脑片上的前额叶神经元，并测定其对胆碱能激动剂卡巴胆碱(CAR)的反应。有三种类型的反应：抑制性(55.3%)、兴奋性(31.1%)和双相(快抑制后慢兴奋，6.8%)，而6.8%的细胞没有反应。CAR抑制的前额叶神经元所占比例随发育而增加。使用胆碱能拮抗剂的实验表明，M2受体介导了抑制反应，而兴奋调制涉及M1、尼古丁，可能还有M3或M5受体，而双相反应是由多种类型的M受体激活引起的。与CAR抑制细胞相比，CAR刺激的PF细胞表现出1)膜时间常数降低，2)超极化激活通道密度(I(H))增加，3)输入电阻(R(In))降低，4)动作电位阈值降低，5)动作电位半宽时程缩短。部分PF细胞呈小穗状，且均受CAR刺激。在发育过程中，我们观察到I(H)密度、R(In)、时间常数和动作电位半宽度减少。这些结果表明，胆碱能调节的PF不同地影响不同的人群，可能包括电耦合细胞。在REM睡眠发育性下降的过程中，PF细胞的兴奋性和胆碱能活性往往降低。
Parafascicular (Pf) neurons receive cholinergic input from the pedunculopontine nucleus (PPN), which is active during waking and REM sleep. There is a developmental decrease in REM sleep in humans between birth and puberty and 10-30 days in rat. Previous studies have established an increase in muscarinic and 5-HT1 serotonergic receptor-mediated inhibition and a transition from excitatory to inhibitory GABA(A) responses in the PPN during the developmental decrease in REM sleep. However, no studies have been conducted on the responses of Pf cells to the cholinergic input from the PPN during development, which is a major target of ascending cholinergic projections and may be an important mechanism for the generation of rhythmic oscillations in the cortex. Whole cell patch-clamp recordings were performed in 9- to 20-day-old rat Pf neurons in parasagittal slices, and responses to the cholinergic agonist carbachol (CAR) were determined. Three types of responses were identified: inhibitory (55.3%), excitatory (31.1%), and biphasic (fast inhibitory followed by slow excitatory, 6.8%), whereas 6.8% of cells showed no response. The proportion of CAR-inhibited Pf neurons increased with development. Experiments using cholinergic antagonists showed that M2 receptors mediated the inhibitory response, whereas excitatory modulation involved M1, nicotinic, and probably M3 or M5 receptors, and the biphasic response was caused by the activation of multiple types of muscarinic receptors. Compared with CAR-inhibited cells, CAR-excited Pf cells showed 1) a decreased membrane time constant, 2) higher density of hyperpolarization-activated channels (I(h)), 3) lower input resistance (R(in)), 4) lower action potential threshold, and 5) shorter half-width duration of action potentials. Some Pf cells exhibited spikelets, and all were excited by CAR. During development, we observed decreases in I(h) density, R(in), time constant, and action potential half-width. These results suggest that cholinergic modulation of Pf differentially affects separate populations, perhaps including electrically coupled cells. Pf cells tend to show decreased excitability and cholinergic activation during the developmental decrease in REM sleep.