Cortical control of affective networks.
Cortical control of affective networks.
复制标题
DOI：
10.1523/jneurosci.0092-12.2013
复制
发表时间：
2013-01-16
期刊：
影响因子：
--
通讯作者：
Dzirasa K
中科院分区：
文献类型：
--
作者：
Kumar S;Black SJ;Hultman R;Szabo ST;DeMaio KD;Du J;Katz BM;Feng G;Covington HE 3rd;Dzirasa K
经颅磁刺激和脑深部电刺激已经成为治疗难治性抑郁症的治疗方式;然而，关于介导这些方法的治疗效果的电路仍然知之甚少。在这里，我们表明，直接光遗传学刺激前额叶皮层（PFC）下降投射神经元的小鼠工程表达Chr 2层锥体神经元（Thy 1-Chr 2小鼠）模型的抗抑郁症样作用的小鼠进行强迫游泳测试。此外，我们表明，这种PFC刺激诱导了社会应激Thy 1-Chr 2小鼠的焦虑样行为（但不是条件性社交回避）的持久抑制：最后一次刺激后>10天观察到的效果。最后，我们同时使用光遗传学刺激和多回路记录技术在Thy 1-Chr 2小鼠中证明皮质投射神经元的激活会引起神经振荡活动，并驱动调节情感的边缘脑区域的同步。重要的是，这些神经振荡的变化直接与时间上精确的激活和抑制边缘单元的活动。总之，我们的研究结果表明，皮层投射系统的直接激活足以调节情感调节网络的活动。他们还表明，皮质投射系统的光遗传学刺激可能作为治疗情感障碍的可行治疗策略。
Transcranial magnetic stimulation and deep brain stimulation have emerged as therapeutic modalities for treatment refractory depression; however, little remains known regarding the circuitry that mediates the therapeutic effect of these approaches. Here we show that direct optogenetic stimulation of prefrontal cortex (PFC) descending projection neurons in mice engineered to express Chr2 in layer V pyramidal neurons (Thy1–Chr2 mice) models an antidepressant-like effect in mice subjected to a forced-swim test. Furthermore, we show that this PFC stimulation induces a long-lasting suppression of anxiety-like behavior (but not conditioned social avoidance) in socially stressed Thy1–Chr2 mice: an effect that is observed >10 d after the last stimulation. Finally, we use optogenetic stimulation and multicircuit recording techniques concurrently in Thy1–Chr2 mice to demonstrate that activation of cortical projection neurons entrains neural oscillatory activity and drives synchrony across limbic brain areas that regulate affect. Importantly, these neural oscillatory changes directly correlate with the temporally precise activation and suppression of limbic unit activity. Together, our findings show that the direct activation of cortical projection systems is sufficient to modulate activity across networks underlying affective regulation. They also suggest that optogenetic stimulation of cortical projection systems may serve as a viable therapeutic strategy for treating affective disorders.