Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear
Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear
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DOI：
10.1073/pnas.1200782109
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发表时间：
2012-05-29
影响因子：
11.1
通讯作者：
Quirk, Gregory J.
中科院分区：
文献类型：
--
作者：
Rodriguez-Romaguera, Jose;Do Monte, Fabricio H. M.;Quirk, Gregory J.
腹侧囊/腹侧纹状体（VC/VS）的脑深部电刺激（DBS）可减轻顽固性强迫症（OCD）的症状，但其作用机制尚不清楚。强迫症的特点是回避行为无法消除，DBS可以部分地通过促进恐惧的消除来发挥作用。我们通过使用大鼠的听觉恐惧条件反射来研究这种可能性，其中恐惧消退的回路具有很好的特征。我们发现，DBS的VS（VC/VS同源大鼠）在灭绝训练减少恐惧的表达和加强灭绝记忆。促进灭绝观察到一个特定的区域的背内侧VS，就在前连合;刺激更多的腹外侧网站VS受损的灭绝。DBS的影响不能得到与药理学失活的背内侧VS或腹外侧VS，这表明纹状体外的机制。因此，DBS的背内侧VS（而不是腹外侧VS）增加了表达的可塑性标记在前边缘和边缘下前额叶皮质，眶额皮质，杏仁中央核（外侧分裂），和闰细胞，已知的学习和表达灭绝。促进恐惧消退表明，与临床观察雅阁，DBS可以增强强迫症认知行为疗法的有效性。
Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces symptoms of intractable obsessive-compulsive disorder (OCD), but the mechanism of action is unknown. OCD is characterized by avoidance behaviors that fail to extinguish, and DBS could act, in part, by facilitating extinction of fear. We investigated this possibility by using auditory fear conditioning in rats, for which the circuits of fear extinction are well characterized. We found that DBS of the VS (the VC/VS homolog in rats) during extinction training reduced fear expression and strengthened extinction memory. Facilitation of extinction was observed for a specific zone of dorsomedial VS, just above the anterior commissure; stimulation of more ventrolateral sites in VS impaired extinction. DBS effects could not be obtained with pharmacological inactivation of either dorsomedial VS or ventrolateral VS, suggesting an extrastriatal mechanism. Accordingly, DBS of dorsomedial VS (but not ventrolateral VS) increased expression of a plasticity marker in the prelimbic and infralimbic prefrontal cortices, the orbitofrontal cortex, the amygdala central nucleus (lateral division), and intercalated cells, areas known to learn and express extinction. Facilitation of fear extinction suggests that, in accord with clinical observations, DBS could augment the effectiveness of cognitive behavioral therapies for OCD.