Celada Pau, Puig M. Victoria, Martín-Ruiz Raúl, Casanovas Josep M., Artigas Francesc
Department of Neurochemistry, Institut d'Investigacions Biomèdiques de Barcelona, CSIC (IDIBAPS), Rosselló 161, 08036 Barcelona, Spain.
Neurotox Res. 2002 Aug-Sep;4(5-6):409-419. doi: 10.1080/10298420290030550.
The prefrontal cortex is involved in an array of higher brain functions that are altered in psychiatric disorders. Serotonergic neurons of the midbrain rapbe nuclei innervate the prefrontal cortex and are the cellular target for drugs used to treat mood disorders such as the selective serotonin (5-HT) reuptake inhibitors. Anatomical evidence supports the existence of projections from the medial prefrontal cortex (mPFC) to the dorsal raphe nucleus (DR). We report on a functional control of the activity of DR 5-HT neurons by projection neurons in the mPFC. The stimulation of the mPFC elicits two types of responses in DR 5-HT neurons, orthodromic excitations and inhibitions. Excitations are mediated by AMPA/KA and NMDA receptors whereas inhibitions are mediated by GABA(A) and 5-HT(1A) receptors. The activation of a subgroup of 5-HT neurons increases 5-HT release which subsequently activates 5-HT(1A) autoreceptors on other 5-HT neurons. GABA(A)-mediated inhibitions involve GABAergic elements in the DR or adjacent areas. Pyramidal neurons of the mPFC co-express postsynaptic 5-HT(1A) (inhibitory) and 5-HT(2A) (excitatory) receptors. Consistent with the above observations, the selective activation of both receptors in mPFC reduced and increased, respectively, the firing activity of DR 5-HT neurons and the 5-HT release in mPFC. Overall, these data indicate that the activity of the 5-HT system is strongly controlled by the mPFC. Thus, the abnormal prefrontal function in post-traumatic stress disorder and depressive patients may induce a disregulation of 5-HT neurons projecting to other brain areas that can underlie the existing symptomatology in these psychiatric disorders.
前额叶皮质参与了一系列在精神疾病中会发生改变的高级脑功能。中脑缝核的5-羟色胺能神经元支配前额叶皮质，并且是用于治疗情绪障碍的药物（如选择性5-羟色胺（5-HT）再摄取抑制剂）的细胞靶点。解剖学证据支持存在从前额叶内侧皮质（mPFC）到中缝背核（DR）的投射。我们报告了mPFC中的投射神经元对DR 5-HT神经元活动的功能控制。mPFC的刺激在DR 5-HT神经元中引发两种类型的反应，即顺向兴奋和抑制。兴奋由AMPA/KA和NMDA受体介导，而抑制由GABA(A)和5-HT(1A)受体介导。一组5-HT神经元的激活会增加5-HT释放，随后激活其他5-HT神经元上的5-HT(1A)自身受体。GABA(A)介导的抑制涉及DR或相邻区域的GABA能元件。mPFC的锥体神经元共表达突触后5-HT(1A)（抑制性）和5-HT(2A)（兴奋性）受体。与上述观察结果一致，mPFC中这两种受体的选择性激活分别降低和增加了DR 5-HT神经元的放电活动以及mPFC中的5-HT释放。总体而言，这些数据表明5-HT系统的活动受到mPFC的强烈控制。因此，创伤后应激障碍和抑郁症患者前额叶功能异常可能会导致投射到其他脑区的5-HT神经元失调，这可能是这些精神疾病现有症状的基础。
