Devoght Jens, Comhair Joris, Morelli Giovanni, Rigo Jean-Michel, D'Hooge Rudi, Touma Chadi, Palme Rupert, Dewachter Ilse, vandeVen Martin, Harvey Robert J, Schiffmann Serge N, Piccart Elisabeth, Brône Bert
Department of Neuroscience, UHasselt, 3500 Hasselt, Belgium.
Brain Development and Disease Laboratory, Instituto Italiano di Tecnologia, 16163 Genova, Italy.
iScience. 2023 Jul 17;26(8):107400. doi: 10.1016/j.isci.2023.107400. eCollection 2023 Aug 18.
The glycine receptor alpha 2 (GlyRα2) is a ligand-gated ion channel which upon activation induces a chloride conductance. Here, we investigated the role of GlyRα2 in dopamine-stimulated striatal cell activity and behavior. We show that depletion of GlyRα2 enhances dopamine-induced increases in the activity of putative dopamine D1 receptor-expressing striatal projection neurons, but does not alter midbrain dopamine neuron activity. We next show that the locomotor response to d-amphetamine is enhanced in GlyRα2 knockout animals, and that this increase correlates with c-fos expression in the dorsal striatum. 3-D modeling revealed an increase in the neuronal ensemble size in the striatum in response to D-amphetamine in GlyRα2 KO mice. Finally, we show enhanced appetitive conditioning in GlyRα2 KO animals that is likely due to increased motivation, but not changes in associative learning or hedonic response. Taken together, we show that GlyRα2 is an important regulator of dopamine-stimulated striatal activity and function.
甘氨酸受体α2（GlyRα2）是一种配体门控离子通道，激活后可诱导氯离子传导。在此，我们研究了GlyRα2在多巴胺刺激的纹状体细胞活性和行为中的作用。我们发现，GlyRα2的缺失增强了多巴胺诱导的假定表达多巴胺D1受体的纹状体投射神经元活性的增加，但不改变中脑多巴胺神经元的活性。接下来，我们表明，在GlyRα2基因敲除动物中，对d-苯丙胺的运动反应增强，并且这种增加与背侧纹状体中的c-fos表达相关。三维建模显示，在GlyRα2基因敲除小鼠中，纹状体中神经元集合大小因D-苯丙胺而增加。最后，我们表明，GlyRα2基因敲除动物的食欲条件反射增强，这可能是由于动机增加，而不是联想学习或享乐反应的改变。综上所述，我们表明GlyRα2是多巴胺刺激的纹状体活性和功能的重要调节因子。
