Role of Striatopallidal Neurons in Drug-Induced Neural Plasticity and Behavior

纹状体主要由GABA能中棘突投射神经元(MSN)组成，但厚度不同 神经肽的表达并形成两种主要的传出途径。含有神经肽的MSN 强啡肽和P物质是纹状体黑质通路的一部分，而MSN包含 神经肽Enl&lt；Ephalin是纹状体或间接途径的一部分。精神刺激剂诱导 纹状体的改变被认为在药物成瘾的发展和维持中起关键作用； 然而，特定的纹状体细胞群的作用尚不清楚。尽管如此，最近的证据表明 纹状体丘脑神经元可能对大脑和行为产生的长期变化特别重要 被毒品迷住。例如，使用早期即时基因表达作为神经元活动指标的研究 研究发现，虽然仅仅是精神刺激剂的暴露就足以增加纹状体黑质神经元的活性，但只有 在导致药物诱导的行为可塑性的条件下暴露于药物，例如 精神运动敏感化，也激活纹状体丘脑神经元。建议的总体目标是 实验是使用新的分子和基因靶向方法来直接检查参与 纹状体甲状旁腺素在药物诱导的分子变化和行为可塑性中的作用。据推测， 纹状体桥脑神经元的重新募集对纹状体基因表达的长期变化至关重要 通过精神刺激剂，以及在精神运动敏感化的发展和表达中， 药品自我管理行为升级。这项工作将有助于阐明 纹状体皮质在成瘾过程中有中等刺状神经元；此外，精确的 识别调节成瘾转变的神经回路应该有助于指导 成瘾者未来治疗方法的发展。

Tlie striatum is mostly comprised of GABAergic medium spiny projection neurons (MSNs) tlnat differ in thieir neuropeptide expression and form two major efferent patiiways. MSNs that contain the neuropeptides dynorptiin and substance P are part of the striatonigral, or 'direct', pathway whereas MSNs that contain the neuropeptide enl<ephalin are part of the striatopallidai, or 'indirect', pathway. Psychostimulant-induced alterations in the striatum are thought to be critical in the development and maintenance of drug addiction; however, the role of specific striatal cell populations is not clear. Nonetheless, recent evidence suggests that striatopallidai neurons may be especially important for the long-term changes in brain and behavior produced by drugs. For example, studies using immediate early gene expression as an indicator of neuronal activity found that while mere psychostimulant exposure is sufficient to increase activity in striatonigral neurons, only drug exposure under conditions that lead to forms of drug-induced behavioral plasticity, such as psychomotor sensitization, also activates striatopallidai neurons. The overall aim of the proposed experiments is to use novel molecular and genetic targeting approaches to directly examine the involvement of striatopallidai MSNs in drug-induced molecular changes and behavioral plasticity. It is hypothesized that recruitment of striatopallidai neurons is critical for the long-term changes in striatal gene expression induced by psychostimulants, as well as in the development and expression of psychomotor sensitization and the escalation of drug self-administration behavior. This work will help to elucidate the contribution of striatopallidai medium spiny neurons in the processes that underlie addiction; In addition, precise identification ofthe neural circuits that regulate the transition to addiction should be useful for guiding the development of future treatments for addicts.