Department of Psychiatry, University of North Carolina Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Biol Psychiatry. 2012 Jun 15;71(12):1061-7. doi: 10.1016/j.biopsych.2011.11.010. Epub 2011 Dec 22.
The manifestation of complex neuropsychiatric disorders, such as drug and alcohol addiction, is thought to result from progressive maladaptive alterations in neural circuit function. Clearly, repeated drug exposure alters a distributed network of neural circuit elements. However, a more precise understanding of addiction has been hampered by an inability to control and, consequently, identify specific circuit components that underlie addictive behaviors. The development of optogenetic strategies for selectively modulating the activity of genetically defined neuronal populations has provided a means for determining the relationship between circuit function and behavior with a level of precision that has been previously unobtainable. Here, we briefly review the main optogenetic studies that have contributed to elucidate neural circuit connectivity within the ventral tegmental area and the nucleus accumbens, two brain nuclei that are essential for the manifestation of addiction-related behaviors. Additional targeted manipulation of genetically defined neural populations in these brain regions, as well as afferent and efferent structures, promises to delineate the cellular mechanisms and circuit components required for the transition from natural goal-directed behavior to compulsive reward seeking despite negative consequences.
复杂神经精神疾病的表现，如药物和酒精成瘾，被认为是由于神经回路功能的进行性适应不良改变所致。显然，反复的药物暴露会改变神经网络元件的分布。然而，由于无法控制和因此无法识别潜在成瘾行为的特定回路成分，对成瘾的更精确理解受到了阻碍。用于选择性调节遗传定义的神经元群体活性的光遗传学策略的发展为确定回路功能与行为之间的关系提供了一种以前无法获得的精确方法。在这里，我们简要回顾了主要的光遗传学研究，这些研究有助于阐明腹侧被盖区和伏隔核内的神经回路连接，这两个脑核对于表现出与成瘾相关的行为至关重要。对这些脑区以及传入和传出结构中的遗传定义的神经群体进行额外的靶向操作，有望描绘出从自然目标导向行为到强迫性寻求奖励的转变所需的细胞机制和回路成分，尽管存在负面后果。
