Graduate Program in Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Departments of Pediatrics and Psychiatry and Behavioral Sciences, Emory University School of Medicine, Emory University, Atlanta, GA, USA.
Sci Rep. 2018 Mar 14;8(1):4495. doi: 10.1038/s41598-018-22560-x.
Specific corticostriatal structures and circuits are important for flexibly shifting between goal-oriented versus habitual behaviors. For example, the orbitofrontal cortex and dorsomedial striatum are critical for goal-directed action, while the dorsolateral striatum supports habits. To determine the role of neurotrophin signaling, we overexpressed a truncated, inactive form of tropomyosin receptor kinase B [also called tyrosine receptor kinase B (TrkB)], the high-affinity receptor for Brain-derived Neurotrophic Factor, in the orbitofrontal cortex, dorsomedial striatum and dorsolateral striatum. Overexpression of truncated TrkB interfered with phosphorylation of full-length TrkB and ERK42/44, as expected. In the orbitofrontal cortex and dorsomedial striatum, truncated trkB overexpression also occluded the ability of mice to select actions based on the likelihood that they would be reinforced. Meanwhile, in the dorsolateral striatum, truncated trkB blocked the development of habits. Thus, corticostriatal TrkB-mediated plasticity appears necessary for balancing actions and habits.
特定的皮质纹状体结构和回路对于灵活地在目标导向行为与习惯行为之间转换很重要。例如，眶额皮层和背内侧纹状体对于目标导向的行动至关重要，而背外侧纹状体则支持习惯。为了确定神经营养因子信号的作用，我们在眶额皮层、背内侧纹状体和背外侧纹状体中超表达了一种截断的、无活性的原肌球蛋白受体激酶 B（也称为酪氨酸受体激酶 B（TrkB）），这是脑源性神经营养因子的高亲和力受体。截断的 TrkB 的过表达如预期的那样干扰全长 TrkB 和 ERK42/44 的磷酸化。在眶额皮层和背内侧纹状体中，截断的 trkB 过表达也阻止了小鼠根据它们被强化的可能性来选择行为的能力。同时，在背外侧纹状体中，截断的 trkB 阻断了习惯的形成。因此，皮质纹状体 TrkB 介导的可塑性似乎对于平衡动作和习惯至关重要。
