Inhibition of dopamine release via presynaptic D2 receptors:: Time course and functional characteristics in vivo
Inhibition of dopamine release via presynaptic D2 receptors:: Time course and functional characteristics in vivo
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DOI：
10.1523/jneurosci.21-23-09134.2001
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发表时间：
2001-12-01
影响因子：
5.3
通讯作者：
Gonon, F
中科院分区：
文献类型：
--
作者：
Benoit-Marand, M;Borrelli, E;Gonon, F
大多数神经递质通过自身受体抑制自身的释放。然而，这些突触前抑制的生理功能仍然知之甚少，部分原因是它们的时间过程和功能特征尚未在体内描述。多巴胺通过D2自身受体抑制自身的释放。在这里，在体内真实的时间内研究了自抑制在冲动流和多巴胺释放之间的关系中所起的作用。多巴胺的释放被诱发在纹状体的麻醉小鼠的内侧前脑束的电刺激，并连续监测安培法使用碳纤维电极。在缺乏D2受体的小鼠中进行的对照实验显示多巴胺释放没有自动抑制。在野生型小鼠中，在100 Hz下用2至6个脉冲刺激线性抑制进一步释放，而单脉冲则效率低下。多巴胺能神经元表现出两种放电模式：在4 Hz以下形成强直活动的单个棘波和在15 Hz下形成2至6个动作电位的爆发。模拟一个脉冲串（15 Hz的四个脉冲）的刺激促进细胞外多巴胺积累，从而抑制多巴胺的进一步释放。这种自抑制在刺激后150和300毫秒之间最大，并在600毫秒内消失。这种延迟和延长的时间过程并没有反映在细胞外DA的可用性，因此可能归因于自受体刺激下游的机制。因此，在生理条件下，自抑制有两个重要的作用。首先，它有助于在爆发期间细胞外多巴胺的衰减。第二，由一个爆发引起的自身抑制瞬时地减弱由紧张性活动引起的进一步多巴胺释放。
Most neurotransmitters inhibit their own release through autoreceptors. However, the physiological functions of these presynaptic inhibitions are still poorly understood, in part because their time course and functional characteristics have not been described in vivo. Dopamine inhibits its own release through D2 autoreceptors. Here, the part played by autoinhibition in the relationship between impulse flow and dopamine release was studied in vivo in real time. Dopamine release was evoked in the striatum of anesthetized mice by electrical stimulation of the medial forebrain bundle and was continuously monitored by amperometry using carbon fiber electrodes. Control experiments performed in mice lacking D2 receptors showed no autoinhibition of dopamine release. In wild-type mice, stimulation at 100 Hz with two to six pulses linearly inhibited further release, whereas single pulses were inefficient. Dopaminergic neurons exhibit two discharge patterns: single spikes forming a tonic activity below 4 Hz and bursts of two to six action potentials at 15 Hz. Stimulation mimicking one burst (four pulses at 15 Hz) promoted extracellular dopamine accumulation and thus inhibited further dopamine release. This autoinhibition was maximal between 150 and 300 msec after stimulation and disappeared within 600 msec. This delayed and prolonged time course is not reflected in extracellular DA availability and thus probably attributable to mechanisms downstream from autoreceptor stimulation. Thus, in physiological conditions, autoinhibition has two important roles. First, it contributes to the attenuation of extracellular dopamine during bursts. Second, autoinhibition elicited by one burst transiently attenuates further dopamine release elicited by tonic activity.