Incubation of palatable food craving is associated with brain-wide neuronal activation in mice.
Incubation of palatable food craving is associated with brain-wide neuronal activation in mice.
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DOI：
10.1073/pnas.2209382119
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发表时间：
2022-11-08
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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在禁欲期间，重新寻求奖励的行为逐渐增加，这种行为现象被称为“渴望的孵化”。潜伏期的机制研究可以带来新的复发治疗方法。然而，由于之前的研究主要使用大鼠模型和有针对性的逐区域分析，因此缺乏奖励寻求孵化的全脑功能图谱。我们建立了小鼠寻找可口食物的孵化行为程序，并使用神经元活动标记 Fos 进行全脑活动映射，以识别该孵化的全脑特征。与大鼠一样，小鼠在禁欲期间也会表现出寻找食物的潜伏期。使用两种互补的活动映射方法，我们发现了一种全脑神经激活增加的模式，该模式反映了禁欲 60 天（而不是 1 或 15 天）后寻找食物的潜伏期。使用啮齿动物模型的研究表明，在戒断期间，药物或食物的复发率逐渐增加，这种行为现象被称为“渴望的孵化”。对渴望产生的机制研究主要集中在预先选定的大脑区域内的特定神经生物学目标。全脑免疫组织化学、透明化和成像方面的最新方法学进展现在可以对学习行为期间参与的区域和回路进行无偏差的全脑细胞分辨率绘图。然而，这些全脑成像方法是针对小鼠大脑开发的，而药物渴望的孵化主要是在大鼠中研究的，而食物渴望的孵化尚未在小鼠中得到证实。在这里，我们建立了一个孵化对美味食物的渴望的小鼠模型，并检查了禁欲 1、15 和 60 天后对食物奖励的寻求。然后，我们使用神经元活动标记 Fos 和完整大脑绘图程序来识别全脑激活的相应模式。戒断 60 天后，与戒断 1 天或 15 天后相比，重新寻求食物的情况明显更高。使用无偏见的 ClearMap 分析，我们发现在 60 天（而不是 1 天或 15 天）禁欲后，多个大脑区域的激活增加，特别是皮质纹状体结构。我们使用正交 SMART2 分析来确认皮质纹状体和丘脑皮质亚体积内的这些发现，并应用专家指导的配准来研究细分和特定层的激活模式。总体而言，我们1）使用补充分析方法确定了食物寻求孵化过程中的全脑活动模式，2）提供了单细胞分辨率的全脑图谱，可用于识别食物渴望孵化过程中的功能网络和全局结构。
Relapse to reward seeking progressively increases during abstinence, a behavioral phenomenon termed “incubation of craving.” Mechanistic studies of incubation can lead to novel relapse treatments. However, as previous studies primarily used rat models and targeted region-by-region analyses, a brain-wide functional atlas of incubation of reward seeking is lacking. We established a behavioral procedure for incubation of palatable food seeking in mice and performed whole-brain activity mapping using the neuronal activity marker Fos to identify the brain-wide signature of this incubation. Like rats, mice showed incubation of food seeking during abstinence. Using two complementary activity mapping approaches, we identified a brain-wide pattern of increased neural activation that mirrored incubation of food seeking after 60 but not 1 or 15 abstinence days. Studies using rodent models have shown that relapse to drug or food seeking increases progressively during abstinence, a behavioral phenomenon termed “incubation of craving.” Mechanistic studies of incubation of craving have focused on specific neurobiological targets within preselected brain areas. Recent methodological advances in whole-brain immunohistochemistry, clearing, and imaging now allow unbiased brain-wide cellular resolution mapping of regions and circuits engaged during learned behaviors. However, these whole-brain imaging approaches were developed for mouse brains, while incubation of drug craving has primarily been studied in rats, and incubation of food craving has not been demonstrated in mice. Here, we established a mouse model of incubation of palatable food craving and examined food reward seeking after 1, 15, and 60 abstinence days. We then used the neuronal activity marker Fos with intact-brain mapping procedures to identify corresponding patterns of brain-wide activation. Relapse to food seeking was significantly higher after 60 abstinence days than after 1 or 15 days. Using unbiased ClearMap analysis, we identified increased activation of multiple brain regions, particularly corticostriatal structures, following 60 but not 1 or 15 abstinence days. We used orthogonal SMART2 analysis to confirm these findings within corticostriatal and thalamocortical subvolumes and applied expert-guided registration to investigate subdivision and layer-specific activation patterns. Overall, we 1) identified brain-wide activity patterns during incubation of food seeking using complementary analytical approaches and 2) provide a single-cell resolution whole-brain atlas that can be used to identify functional networks and global architecture underlying the incubation of food craving.
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DOI：
10.1523/jneurosci.1914-12.2012
发表时间：
2012-08-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fanous S;Goldart EM;Theberge FR;Bossert JM;Shaham Y;Hope BT
通讯作者：
Hope BT
影响因子：
3.3
作者：
Blackwood, Christopher A.;Leary, Michael;Cadet, Jean Lud
通讯作者：
Cadet, Jean Lud
影响因子：
5.3
作者：
Golden, Sam A.;Jin, Michelle;Shaham, Yavin
通讯作者：
Shaham, Yavin
影响因子：
5.6
作者：
Bienkowski, P;Rogowski, A;Kostowski, W
通讯作者：
Kostowski, W
影响因子：
5.3
作者：
Golden, Sam A.;Jin, Michelle;Shaham, Yavin
通讯作者：
Shaham, Yavin