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背外侧被盖区到伏隔核投射的损伤导致糖皮质激素触发的奖赏缺陷。

Impairments in laterodorsal tegmentum to VTA projections underlie glucocorticoid-triggered reward deficits.

机构信息

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.

ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.

出版信息

Elife. 2017 Aug 24;6:e25843. doi: 10.7554/eLife.25843.

DOI:10.7554/eLife.25843
PMID:28837419
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5576484/
Abstract

Ventral tegmental area (VTA) activity is critical for reward/reinforcement and is tightly modulated by the laterodorsal tegmentum (LDT). exposure to glucocorticoids (iuGC) triggers prominent motivation deficits but nothing is known about the impact of this exposure in the LDT-VTA circuit. We show that iuGC-rats have long-lasting changes in cholinergic markers in the LDT, together with a decrease in LDT basal neuronal activity. Interestingly, upon LDT stimulation, iuGC animals present a decrease in the magnitude of excitation and an increase in VTA inhibition, as a result of a shift in the type of cells that respond to the stimulus. In agreement with LDT-VTA dysfunction, we show that iuGC animals present motivational deficits that are rescued by selective optogenetic activation of this pathway. Importantly, we also show that LDT-VTA optogenetic stimulation is reinforcing, and that iuGC animals are more susceptible to the reinforcing properties of LDT-VTA stimulation.

摘要

腹侧被盖区（VTA）的活动对奖励/强化至关重要，并且受到外侧背侧被盖区（LDT）的紧密调节。糖皮质激素（iuGC）的暴露会引发明显的动机缺陷，但对于这种暴露对 LDT-VTA 回路的影响却一无所知。我们发现，iuGC 大鼠的 LDT 中的胆碱能标志物出现持久变化，同时 LDT 基础神经元活性下降。有趣的是，LDT 刺激时，iuGC 动物表现出兴奋幅度减小，VTA 抑制增加，这是由于对刺激做出反应的细胞类型发生了转变。与 LDT-VTA 功能障碍一致，我们发现 iuGC 动物表现出动机缺陷，而选择性光遗传激活该通路可挽救这些缺陷。重要的是，我们还发现 LDT-VTA 的光遗传刺激具有强化作用，而 iuGC 动物对 LDT-VTA 刺激的强化作用更为敏感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/8c2d90f1c6a4/elife-25843-fig4-figsupp3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/89eb5313cc89/elife-25843-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/ee65912edb3e/elife-25843-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/37fe23e72098/elife-25843-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/38e6bfe5bfe6/elife-25843-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/ef222d227147/elife-25843-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/ab282e7a798e/elife-25843-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/8c2d90f1c6a4/elife-25843-fig4-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/ce0ef96b78b2/elife-25843-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/5bc8a7a859ba/elife-25843-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/78b22d958dec/elife-25843-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/2c48889e6670/elife-25843-fig1-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/89eb5313cc89/elife-25843-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/ee65912edb3e/elife-25843-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/37fe23e72098/elife-25843-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/38e6bfe5bfe6/elife-25843-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/ef222d227147/elife-25843-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/ab282e7a798e/elife-25843-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/5576484/8c2d90f1c6a4/elife-25843-fig4-figsupp3.jpg

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