Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, 55 Wade Ave., Catonsville, MD 21228, USA.
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, 55 Wade Ave., Catonsville, MD 21228, USA.
Neuroscience. 2024 May 24;547:56-73. doi: 10.1016/j.neuroscience.2024.04.005. Epub 2024 Apr 16.
Dopamine (DA) neurons of the substantia nigra (SN) and ventral tegmental area generally respond to aversive stimuli or the absence of expected rewards with transient inhibition of firing rates, which can be recapitulated with activation of the lateral habenula (LHb) and eliminated by lesioning the intermediating rostromedial tegmental nucleus (RMTg). However, a minority of DA neurons respond to aversive stimuli, such as foot shock, with a transient increase in firing rate, an outcome that rarely occurs with LHb stimulation. The degree to which individual neurons respond to these two stimulation modalities with the same response phenotype and the role of the RMTg is not known. Here, we record responses from single SN DA neurons to alternating activation of the LHb and foot shock in male rats. Lesions of the RMTg resulted in a shift away from inhibition to no response during both foot shock and LHb stimulation. Furthermore, lesions unmasked an excitatory response during LHb stimulation. The response correspondence within the same neuron between the two activation sources was no different from chance in sham controls, suggesting that external inputs rather than intrinsic DA neuronal properties are more important to response outcome. These findings contribute to a literature that shows a complex neurocircuitry underlies the regulation of DA activity and, by extension, behaviors related to learning, anhedonia, and cognition.
中脑黑质 (SN) 和腹侧被盖区的多巴胺 (DA) 神经元通常会对厌恶刺激或预期奖励的缺失做出短暂的反应,即发射率的抑制,这可以通过激活外侧缰核 (LHb) 来重现,也可以通过损伤中间的穹隆脚间核 (RMTg) 来消除。然而,少数 DA 神经元对厌恶刺激(如足底电击)的反应是发射率的短暂增加,这种结果很少发生在 LHb 刺激时。个体神经元对这两种刺激模式的反应程度是否具有相同的反应表型以及 RMTg 的作用尚不清楚。在这里,我们记录了雄性大鼠 SN DA 神经元对交替激活 LHb 和足底电击的反应。RMTg 的损伤导致在足底电击和 LHb 刺激期间,从抑制转变为无反应。此外,损伤还揭示了在 LHb 刺激期间的兴奋反应。在假手术对照组中,两个激活源之间相同神经元的反应对应性与随机无差别,这表明外部输入而不是内在的 DA 神经元特性对反应结果更为重要。这些发现为文献提供了贡献,表明复杂的神经回路是调节 DA 活动的基础,进而与学习、快感缺失和认知相关的行为有关。