Trantham-Davidson Heather, Kröner Sven, Seamans Jeremy K
Medical University of South Carolina, Department of Neuroscience, BSB 403, 173 Ashley Avenue, Charleston, SC 29425, USA.
Cereb Cortex. 2008 Apr;18(4):951-8. doi: 10.1093/cercor/bhm133. Epub 2007 Aug 9.
Dopamine (DA) exerts a strong influence on inhibition in prefrontal cortex. The main cortical interneuron subtype targeted by DA are fast-spiking gamma-aminobutyric acidergic (GABAergic) cells that express the calcium-binding protein parvalbumin. D1 stimulation depolarizes these interneurons and increases excitability evoked by current injection. The present study examined whether this direct DA-dependent modulation of fast-spiking interneurons involves DARPP-32. Whole-cell patch-clamp recordings were made from fast-spiking interneurons in brain slices from DARPP-32 knockout (KO) mice, wild-type mice, and rats. Low concentrations of DA (100 nM) increased interneuron excitability via D1 receptors, protein kinase A, and cyclic adenosine 3',5'-monophosphate in slices from both normal and DARPP-32 KO mice. Immunohistochemical staining of slices from normal animals revealed a lack of colocalization of DARPP-32 with calcium-binding proteins selective for fast-spiking interneurons, indicating that these interneurons do not express DARPP-32. Therefore, although DARPP-32 impacts cortical inhibition through a previously demonstrated D2-dependent regulation of GABAergic currents in pyramidal cells, it is not involved in the direct D1-mediated regulation of fast-spiking interneurons.
多巴胺（DA）对前额叶皮质的抑制作用有强烈影响。DA靶向的主要皮质中间神经元亚型是表达钙结合蛋白小白蛋白的快速放电γ-氨基丁酸能（GABAergic）细胞。D1刺激使这些中间神经元去极化，并增加电流注入诱发的兴奋性。本研究探讨这种对快速放电中间神经元的直接DA依赖性调节是否涉及DARPP-32。采用全细胞膜片钳记录技术，分别对DARPP-32基因敲除（KO）小鼠、野生型小鼠和大鼠脑片上的快速放电中间神经元进行记录。低浓度的DA（100 nM）通过D1受体、蛋白激酶A和环磷酸腺苷，增加正常小鼠和DARPP-32 KO小鼠脑片中间神经元的兴奋性。对正常动物脑片进行免疫组织化学染色显示，DARPP-32与快速放电中间神经元选择性钙结合蛋白无共定位，表明这些中间神经元不表达DARPP-32。因此，尽管DARPP-32通过先前证实的对锥体细胞GABA能电流的D2依赖性调节影响皮质抑制，但它不参与对快速放电中间神经元的直接D1介导的调节。
