Lateral habenula stimulation inhibits rat midbrain dopamine neurons through a GABAA receptor-mediated mechanism
Lateral habenula stimulation inhibits rat midbrain dopamine neurons through a GABAA receptor-mediated mechanism
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DOI：
10.1523/jneurosci.0958-07.2007
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发表时间：
2007-06-27
影响因子：
5.3
通讯作者：
Shepard, Paul D.
中科院分区：
文献类型：
--
作者：
Ji, Huifang;Shepard, Paul D.
中脑多巴胺神经元活动的瞬时变化编码一种误差信号，该信号有助于联想学习。尽管人们对导致多巴胺活动阶段性增加的机制给予了相当多的关注，但对于伴随预期奖励意外缺失而出现的放电瞬时停止的起源却知之甚少。最近的研究表明，外侧缰核（LHb）可能在人类的这种信号传递中起作用，这促使我们评估LHb刺激对麻醉大鼠多巴胺和非多巴胺神经元活动的影响。LHb的单脉冲刺激（0.5毫安，100微秒）瞬时抑制了黑质和腹侧被盖区记录到的97%的多巴胺神经元的活动。抑制的持续时间平均约为85毫秒，在这两个区域之间没有差异。相同的刺激瞬时兴奋了腹中脑52%的非多巴胺神经元。缰核脚间束的电解损伤阻断了LHb刺激对多巴胺神经元的影响。局部应用荷包牡丹碱而非SK通道阻滞剂蜂毒明肽减弱了LHb刺激对多巴胺细胞的影响，表明这种反应是由GABA（A）受体介导的。这些数据表明，LHb诱导的多巴胺细胞活动抑制是通过腹中脑假定的GABA能神经元的正向激活间接介导的。缰核 - 中脑通路能够在群体水平上瞬时抑制多巴胺神经元的活动，可能是参与编码奖励预期的电路的一个重要组成部分。
Transient changes in the activity of midbrain dopamine neurons encode an error signal that contributes to associative learning. Although considerable attention has been devoted to the mechanisms contributing to phasic increases in dopamine activity, less is known about the origin of the transient cessation in firing accompanying the unexpected loss of a predicted reward. Recent studies suggesting that the lateral habenula (LHb) may contribute to this type of signaling in humans prompted us to evaluate the effects of LHb stimulation on the activity of dopamine and non- dopamine neurons of the anesthetized rat. Single-pulse stimulation of the LHb (0.5 mA, 100 mu s) transiently suppressed the activity of 97% of the dopamine neurons recorded in the substantia nigra and ventral tegmental area. The duration of the cessation averaged similar to 85 ms and did not differ between the two regions. Identical stimuli transiently excited 52% of the non-dopamine neurons in the ventral midbrain. Electrolytic lesions of the fasciculus retroflexus blocked the effects of LHb stimulation on dopamine neurons. Local application of bicuculline but not the SK-channel blocker apamin attenuated the effects of LHb stimulation on dopamine cells, indicating that the response is mediated by GABA(A) receptors. These data suggest that LHb-induced suppression of dopamine cell activity is mediated indirectly by orthodromic activation of putative GABAergic neurons in the ventral midbrain. The habenulomesencephalic pathway, which is capable of transiently suppressing the activity of dopamine neurons at a population level, may represent an important component of the circuitry involved in encoding reward expectancy.