Food-associated cues alter forebrain functional connectivity as assessed with immediate early gene and proenkephalin expression.

Food-associated cues alter forebrain functional connectivity as assessed with immediate early gene and proenkephalin expression.
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与食物相关的提示改变了前脑功能连通性,如直接的早期基因和原晶蛋白表达所评估。

DOI:
10.1186/1741-7007-5-16
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发表时间:
2007-04-26
期刊:
影响因子:
5.4
通讯作者:
Kelley AE
Kelley AE
中科院分区:
生物学2区
文献类型:
--
作者:
Schiltz CA;Bremer QZ;Landry CF;Kelley AE

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预测食物可获得性的线索是食欲以及寻找食物和摄食行为的强大调节剂。这些条件反射的神经生物学基础还不清楚。监测区域立即早期基因表达是用于评估由上游细胞内和细胞外信号传导引起的神经元代谢改变的方法。此外,评估多个立即早期基因的表达提供了一个窗口,暴露于食物线索的可能后遗症,因为每个基因的功能不同。我们使用即时早期基因和前脑啡肽原表达作为评估食物提示引起的区域激活和前脑功能连接改变的手段。与可口食物相关的情境线索引起大鼠条件性运动激活和皮质酮释放。这种动机状态与皮质边缘、丘脑和下丘脑区域的活动调节基因homer 1a、arc、zif 268、ngfi-b和c-fos以及纹状体区域内的前脑啡肽的转录增加有关。此外,由食物线索引起的功能连接性,如通过区域间多基因表达相关性方法评估的,与由中性线索引起的功能连接性大不相同。具体来说,食物线索增加了纹状体的皮质参与,并在核内,将相关性从外壳转移到核心。暴露于食物相关的背景下也诱导皮质纹状体网络和基底外侧杏仁核之间的相关基因表达,基底外侧杏仁核是学习和响应感官刺激的激励价值的关键区域。这种增加的皮质纹状体-杏仁核功能连接在暴露于无害线索的对照组中是不存在的。结果表明,在产生可能促进过量食物摄入的条件激励状态时,皮质和纹状体之间的相关活动,特别是丘脑核核心和基底外侧杏仁核之间的相关活动。在皮质纹状体、丘脑和下丘脑网络中,许多基因以独特的模式上调,这表明食物线索能够有力地改变调节情绪、认知、唤醒和能量平衡调节的区域中的神经元加工。由于这些基因中的许多在可塑性中发挥作用,它们在这些回路中的上调也可能表明了灭绝学习的神经解剖学和转录相关性。
Cues predictive of food availability are powerful modulators of appetite as well as food-seeking and ingestive behaviors. The neurobiological underpinnings of these conditioned responses are not well understood. Monitoring regional immediate early gene expression is a method used to assess alterations in neuronal metabolism resulting from upstream intracellular and extracellular signaling. Furthermore, assessing the expression of multiple immediate early genes offers a window onto the possible sequelae of exposure to food cues, since the function of each gene differs. We used immediate early gene and proenkephalin expression as a means of assessing food cue-elicited regional activation and alterations in functional connectivity within the forebrain. Contextual cues associated with palatable food elicited conditioned motor activation and corticosterone release in rats. This motivational state was associated with increased transcription of the activity-regulated genes homer1a, arc, zif268, ngfi-b and c-fos in corticolimbic, thalamic and hypothalamic areas and of proenkephalin within striatal regions. Furthermore, the functional connectivity elicited by food cues, as assessed by an inter-regional multigene-expression correlation method, differed substantially from that elicited by neutral cues. Specifically, food cues increased cortical engagement of the striatum, and within the nucleus accumbens, shifted correlations away from the shell towards the core. Exposure to the food-associated context also induced correlated gene expression between corticostriatal networks and the basolateral amygdala, an area critical for learning and responding to the incentive value of sensory stimuli. This increased corticostriatal-amygdalar functional connectivity was absent in the control group exposed to innocuous cues. The results implicate correlated activity between the cortex and the striatum, especially the nucleus accumbens core and the basolateral amygdala, in the generation of a conditioned motivated state that may promote excessive food intake. The upregulation of a number of genes in unique patterns within corticostriatal, thalamic, and hypothalamic networks suggests that food cues are capable of powerfully altering neuronal processing in areas mediating the integration of emotion, cognition, arousal, and the regulation of energy balance. As many of these genes play a role in plasticity, their upregulation within these circuits may also indicate the neuroanatomic and transcriptional correlates of extinction learning.
DOI: 10.1038/35082096
发表时间: 2001-06-21
期刊: NATURE
影响因子: 64.8
作者:
Ango, F;Prézeau, L;Fagni, L
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