López-Terrones Elena, Celada Pau, Riga Maurizio S, Artigas Francesc
Depart. de Neurociències i Terapèutica Experimental, Institut d'Investigacions Biomèdiques de Barcelona, IIBB-CSIC; 08036 Barcelona, Spain.
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Cereb Cortex. 2022 Jul 12;32(14):3000-3013. doi: 10.1093/cercor/bhab396.
The infralimbic (IL) cortex is the rodent equivalent of human ventral anterior cingulate cortex (vACC), which plays a key role in the pathophysiology and treatment of major depressive disorder (MDD). The modulation of glutamatergic neurotransmission in IL [but not in the adjacent prelimbic (PrL) cortex] evokes antidepressant-like or depressive-like behaviors, associated with changes in serotonin (5-HT) function, highlighting the relevance of glutamate/serotonin interactions in IL for emotional control. 5-HT modulates neuronal activity in PrL and cingulate (Cg) cortex but its effects in IL are largely unknown. We therefore compared the in vivo effects of 5-HT on pyramidal neuron activity in IL (n = 61) and PrL (n = 50) of anesthetized rats. IL pyramidal neurons were more responsive to physiological dorsal raphe stimulation (0.9 Hz) than PrL neurons (84% vs. 64%, respectively) and were inhibited to a greater extent (64% vs. 36%, respectively). Orthodromic activations (8% in PrL) were absent in IL, whereas biphasic responses were similar (20%) in both areas. Excitations were mediated by 5-HT2A-R activation, whereas inhibitions involved 3 different components: 5-HT1A-R, 5-HT3-R and GABAA-R, respectively. The remarkable inhibitory action of 5-HT in IL suggests that 5-HT-enhancing drugs may exert their antidepressant action by normalizing a glutamatergic hyperactivity in the vACC of MDD patients.
边缘下（IL）皮质相当于啮齿动物的人类腹侧前扣带回皮质（vACC），其在重度抑郁症（MDD）的病理生理学和治疗中起关键作用。IL中谷氨酸能神经传递的调节（而非相邻的前边缘（PrL）皮质）会引发抗抑郁样或抑郁样行为，这与血清素（5-HT）功能的变化相关，突出了IL中谷氨酸/血清素相互作用对情绪控制的相关性。5-HT调节PrL和扣带回（Cg）皮质中的神经元活动，但其在IL中的作用在很大程度上尚不清楚。因此，我们比较了5-HT对麻醉大鼠IL（n = 61）和PrL（n = 50）中锥体神经元活动的体内影响。IL锥体神经元对生理性中缝背核刺激（0.9 Hz）的反应比PrL神经元更敏感（分别为84%和64%），并且受到的抑制程度更大（分别为64%和36%）。IL中不存在顺向激活（PrL中为8%），而两个区域的双相反应相似（均为20%）。兴奋由5-HT2A-R激活介导，而抑制分别涉及3种不同成分：5-HT1A-R、5-HT3-R和GABAA-R。5-HT在IL中的显著抑制作用表明，增强5-HT的药物可能通过使MDD患者vACC中的谷氨酸能活动亢进正常化来发挥其抗抑郁作用。
