伏隔核
神经科学
中棘神经元
基底外侧杏仁核
边缘下皮质
树突棘
可塑性
有条件地点偏好
眶额皮质
多巴胺
多巴胺受体D2
结构塑性
上瘾
多巴胺受体D1
心理学
化学
海马体
扁桃形结构
前额叶皮质
生物
可卡因依赖
纹状体
海马结构
物理
中枢神经系统
认知
热力学
作者
Cindy Barrientos,Daniel Knowland,Mingche M.J. Wu,Varoth Lilascharoen,Kee Wui Huang,Robert C. Malenka,Byung Kook Lim
标识
DOI:10.1016/j.biopsych.2018.04.019
摘要
Background The nucleus accumbens (NAc) is a brain region implicated in pathological motivated behaviors such as drug addiction and is composed predominantly of two discrete populations of neurons, dopamine receptor-1– and dopamine receptor-2–expressing medium spiny neurons (D1-MSNs and D2-MSNs, respectively). It is unclear whether these populations receive inputs from different brain areas and whether input regions to these cell types undergo distinct structural adaptations in response to the administration of addictive drugs such as cocaine. Methods Using a modified rabies virus–mediated tracing method, we created a comprehensive brain-wide monosynaptic input map to NAc D1- and D2-MSNs. Next, we analyzed nearly 2000 dendrites and 125,000 spines of neurons across four input regions (the prelimbic cortex, medial orbitofrontal cortex, basolateral amygdala, and ventral hippocampus) at four separate time points during cocaine administration and withdrawal to examine changes in spine density in response to repeated intraperitoneal cocaine injection in mice. Results D1- and D2-MSNs display overall similar input profiles, with the exception that D1-MSNs receive significantly more input from the medial orbitofrontal cortex. We found that neurons in distinct brain areas projecting to D1- and D2-MSNs display different adaptations in dendritic spine density at different stages of cocaine administration and withdrawal. Conclusions While NAc D1- and D2-MSNs receive input from similar brain structures, cocaine-induced spine density changes in input regions are quite distinct and dynamic. While previous studies have focused on input-specific postsynaptic changes within NAc MSNs in response to cocaine, these findings emphasize the dramatic changes that occur in the afferent input regions as well.
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