Kiyatkin E A, Rebec G V
Department of Psychology, Indiana University, Bloomington 47405, USA.
Neuroscience. 1998 Aug;85(4):1285-309. doi: 10.1016/s0306-4522(98)00054-2.
Single-unit recording combined with iontophoresis of dopamine, GABA, and glutamate was used in awake, unrestrained rats to characterize the electrophysiological and receptor properties of neurons in the ventral tegmental area under naturally occurring behavioural conditions. All isolated ventral tegmental area units (n=90) were analysed and compared with cells (n=58) recorded from dorsally adjacent areas of the pre-rubral area and red nucleus. Two distinct neuronal groups were identified in the ventral tegmental area: units with triphasic, long-duration spikes (78/90) and units with biphasic, short-duration spikes (12/90). Although all long-spike units discharged in an irregular, bursting pattern with varying degrees of within-burst decrements in spike amplitude, they could be further subdivided into at least three distinct subgroups. Type I long-spike units (36/78) discharged at a relatively slow and stable rate (mean: 6.03 imp/s; range: 0.42-15.78) with no evident fluctuations during movement. These cells were inhibited by dopamine and GABA and responded to glutamate with a low-magnitude excitation accompanied by a pronounced decrement in spike amplitude and a powerful rebound inhibition. Type II long-spike units (23/78) had relatively high and unstable discharge rates (mean: 22.82 imp/s; range: 4.42-59.67) and showed movement-related phasic activations frequently followed by partial or complete cessation of firing. Some Type II cells (4/9) were inhibited by dopamine, but all were excited by glutamate at very low currents (0-10 nA). With an increase in current, the glutamate-induced excitation often (18/22) progressed into a cessation of firing. All these cells were inhibited by GABA followed by a strong rebound excitation (8/9), which also frequently (6/8) resulted in cessation of firing. Type III long-spike units (19/78) had properties that differed from either Type I or Type II cells, including a lack of spontaneous firing (5/19). Short-spike ventral tegmental area units were either silent (4/12) and unresponsive to dopamine and GABA or spontaneously active (range: 0.89-34.13 imp/s) and inhibited by GABA and, in some cases (2/8). by dopamine; all were phasically activated during movement and glutamate iontophoresis. It appears that ventral tegmental area neurons, including those with long-duration spikes, do not comprise a uniform population in awake, unrestrained rats. Type I, long-spike units match the characteristics of histochemically-identified dopamine neurons, and they appear to express dopamine autoreceptors, which may explain the relatively slow, stable rate of activity and the limited responsiveness to excitatory inputs. Although the nature of the other long-spike units in our sample is unclear, they may include dopamine neurons without autoreceptors as well as non-dopamine cells. The heterogeneity of ventral tegmental area neurons is an important consideration for further attempts to assess the role of the mesocorticolimbic dopamine system in motivated behaviour.
在清醒、不受束缚的大鼠中，采用单单位记录结合多巴胺、γ-氨基丁酸（GABA）和谷氨酸的离子导入法，以表征在自然行为条件下腹侧被盖区神经元的电生理和受体特性。对所有分离出的腹侧被盖区单位（n = 90）进行了分析，并与从红核前区背侧相邻区域记录的细胞（n = 58）进行了比较。在腹侧被盖区鉴定出两个不同的神经元群：具有三相、长时程锋电位的单位（78/90）和具有双相、短时程锋电位的单位（12/90）。尽管所有长锋电位单位均以不规则的爆发模式放电，且在爆发内锋电位幅度有不同程度的递减，但它们可进一步细分为至少三个不同的亚群。I型长锋电位单位（36/78）以相对缓慢且稳定的速率放电（平均：6.03次/秒；范围：0.42 - 15.78），在运动过程中无明显波动。这些细胞被多巴胺和GABA抑制，对谷氨酸有低幅度兴奋反应，同时伴有锋电位幅度明显递减和强烈的反弹抑制。II型长锋电位单位（23/78）具有相对较高且不稳定的放电速率（平均：22.82次/秒；范围：4.42 - 59.67），并表现出与运动相关的相位激活，随后常伴有部分或完全停止放电。一些II型细胞（4/9）被多巴胺抑制，但所有细胞在非常低的电流（0 - 10纳安）下都被谷氨酸兴奋。随着电流增加，谷氨酸诱导的兴奋常（18/22）发展为停止放电。所有这些细胞被GABA抑制，随后有强烈的反弹兴奋（8/9），这也常（6/8）导致停止放电。III型长锋电位单位（19/78）具有与I型或II型细胞不同的特性，包括缺乏自发放电（5/19）。短锋电位腹侧被盖区单位要么沉默（4/12），对多巴胺和GABA无反应，要么自发放电（范围：0.89 - 34.13次/秒），并被GABA抑制，在某些情况下（2/8）被多巴胺抑制；所有单位在运动和谷氨酸离子导入过程中均有相位激活。似乎腹侧被盖区神经元，包括那些具有长时程锋电位的神经元，在清醒、不受束缚的大鼠中并非一个均匀的群体。I型长锋电位单位符合组织化学鉴定的多巴胺能神经元的特征，并且它们似乎表达多巴胺自身受体，这可能解释了相对缓慢、稳定的活动速率以及对兴奋性输入的有限反应性。尽管我们样本中其他长锋电位单位的性质尚不清楚，但它们可能包括没有自身受体的多巴胺能神经元以及非多巴胺能细胞。腹侧被盖区神经元的异质性是进一步评估中脑皮质边缘多巴胺系统在动机行为中作用时的一个重要考虑因素。
