Do-Monte Fabricio H, Rodriguez-Romaguera Jose, Rosas-Vidal Luis E, Quirk Gregory J
Departments of Psychiatry and Anatomy and Neurobiology, University of Puerto Rico School of Medicine San Juan, Puerto Rico.
Front Behav Neurosci. 2013 Aug 8;7:102. doi: 10.3389/fnbeh.2013.00102. eCollection 2013.
Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces the symptoms of treatment-resistant obsessive compulsive disorder (OCD), and improves response to extinction-based therapies. We recently reported that DBS-like stimulation of a rat homologue of VC/VS, the dorsal-VS, reduced conditioned fear and enhanced extinction memory (Rodriguez-Romaguera et al., 2012). In contrast, DBS of the ventral-VS had the opposite effects. To examine possible mechanisms of these effects, we assessed the effects of VS DBS on the expression of the neural activity marker Fos and brain-derived neurotrophic factor (BDNF), a key mediator of extinction plasticity in prefrontal-amygdala circuits. Consistent with decreased fear expression, DBS of dorsal-VS increased Fos expression in prelimbic and infralimbic prefrontal cortices and in the lateral division of the central nucleus of amygdala, an area that inhibits amygdala output. Consistent with improved extinction memory, we found that DBS of dorsal-VS, but not ventral-VS, increased neuronal BDNF expression in prelimbic and infralimbic prefrontal cortices. These rodent findings are consistent with the idea that clinical DBS of VC/VS may augment fear extinction through an increase in BDNF expression.
腹侧囊/腹侧纹状体（VC/VS）的深部脑刺激（DBS）可减轻难治性强迫症（OCD）的症状，并改善对基于消退的疗法的反应。我们最近报道，对大鼠VC/VS的同源物背侧纹状体进行类似DBS的刺激，可减少条件性恐惧并增强消退记忆（Rodriguez-Romaguera等人，2012年）。相比之下，腹侧纹状体的DBS则产生相反的效果。为了研究这些效应的可能机制，我们评估了纹状体DBS对神经活动标记物Fos和脑源性神经营养因子（BDNF）表达的影响，BDNF是前额叶-杏仁核回路中消退可塑性的关键介质。与恐惧表达减少一致，背侧纹状体的DBS增加了前边缘和下边缘前额叶皮质以及杏仁核中央核外侧部的Fos表达，杏仁核中央核外侧部是一个抑制杏仁核输出的区域。与消退记忆改善一致，我们发现背侧纹状体而非腹侧纹状体的DBS增加了前边缘和下边缘前额叶皮质中神经元BDNF的表达。这些啮齿动物研究结果与以下观点一致，即临床对VC/VS进行DBS可能通过增加BDNF表达来增强恐惧消退。
