Luo Alice H, Georges François E, Aston-Jones Gary S
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Eur J Neurosci. 2008 Jan;27(2):408-22. doi: 10.1111/j.1460-9568.2007.05985.x.
The ventral tegmental area (VTA) contains dopamine (DA) and gamma-aminobutyric acid (GABA) neurons involved in motivation and behavioral state. These phenomena are also influenced by circadian factors. The goal of our studies was to examine the impulse activity of neurochemically identified VTA neurons during dark (active) vs light (rest) phases of the circadian cycle. Using extracellular single-unit recordings with juxtacellular labeling in anesthetized rats, we found multiple neuronal subpopulations including 'novel neurons' that selectively fired during the dark phase. These novel neurons were electrophysiologically categorized into two groups, 'novel wide-spike' and 'novel thin-spike' neurons. Characterization of novel wide-spike neurons found they were consistently non-dopaminergic and non-GABAergic [tyrosine hydroxylase (TH)(-), glutamic acid decarboxylase (GAD)(-)]. However, they were inhibited by the D2 agonist quinpirole, an effect that could be reversed by the D2 antagonist eticlopride. Physiologically, they were fast firing (mean = 18.9 +/- 1.2 spikes/s), low bursting neurons (median = 6.2 +/- 3.0% of spikes in bursts) with spike durations > or = 2.0 ms, but slightly shorter than TH(+) neurons. They were also consistently non-responsive to footpad stimulation. The novel thin-spike neurons were neurochemically heterogeneous, and were located more ventrally than thin-spike neurons found during the light phase. These findings reveal previously unknown populations of VTA neurons whose activities are sensitive to diurnal phase, and whose functions may be in the temporal regulation of arousal and motivational processes.
腹侧被盖区(VTA)包含参与动机和行为状态的多巴胺(DA)能和γ-氨基丁酸(GABA)能神经元。这些现象也受昼夜节律因素的影响。我们研究的目的是检查在昼夜周期的黑暗(活动)与光照(休息)阶段神经化学鉴定的VTA神经元的冲动活动。在麻醉大鼠中使用细胞外单单位记录并结合细胞旁标记,我们发现了多个神经元亚群,包括在黑暗阶段选择性放电的“新型神经元”。这些新型神经元在电生理上被分为两组,即“新型宽峰”和“新型窄峰”神经元。对新型宽峰神经元的特征分析发现,它们始终是非多巴胺能和非GABA能的[酪氨酸羟化酶(TH)(-),谷氨酸脱羧酶(GAD)(-)]。然而,它们被D2激动剂喹吡罗抑制,这种作用可被D2拮抗剂依替必利逆转。在生理上,它们是快速放电(平均=18.9±1.2个动作电位/秒)、低爆发性的神经元(爆发中动作电位的中位数=6.2±3.0%),动作电位持续时间≥2.0毫秒,但略短于TH(+)神经元。它们对足底刺激也始终无反应。新型窄峰神经元在神经化学上是异质性的,并且比在光照阶段发现的窄峰神经元位于更腹侧的位置。这些发现揭示了以前未知的VTA神经元群体,其活动对昼夜节律敏感,其功能可能在于觉醒和动机过程的时间调节。