Converging evidence that short-active photoperiod increases acetylcholine signaling in the hippocampus.
Converging evidence that short-active photoperiod increases acetylcholine signaling in the hippocampus.
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DOI：
10.3758/s13415-020-00824-2
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Young JW
中科院分区：
文献类型：
--
作者：
Cope ZA;Lavadia ML;Joosen AJM;van de Cappelle CJA;Lara JC;Huval A;Kwiatkowski MK;Picciotto MR;Mineur YS;Dulcis D;Young JW
环境光线的季节性变化影响季节性情感障碍（SAD）和双相情感障碍（BD）情绪之间的转换，抑郁症出现在短暂的活跃（SA）冬季。在健康动物中也可以观察到光引起的行为变化，并且在多巴胺转运体表达减少的小鼠中这种变化会加剧。具体而言，减少小鼠的夜间活动时间（SA）增加了惩罚耐力和强迫游泳测试（FST）不动。用乙酰胆碱酯酶抑制剂毒豆碱升高乙酰胆碱可引起人的抑郁症状，并增加小鼠的FST不动。在概率学习任务和FST测试前，我们利用SA光周期和毒豆碱来提高乙酰胆碱水平，包括用烟碱和东莨菪碱拮抗剂和靶向海马腺相关病毒给药来逆转随后的缺陷。我们证实，在概率学习范式中，芥子碱也增加了惩罚敏感性。此外，毒蕈碱和烟碱受体阻断减弱了毒豆碱和sa诱导的表型。最后，病毒介导的海马乙酰胆碱酯酶表达用于降低乙酰胆碱酯酶水平，阻断sa诱导的FST不动性升高。这些结果表明，海马乙酰胆碱神经传递增加是SA暴露诱导行为表达的必要条件。此外，这些研究支持了胆碱能治疗抑郁症的潜力。综上所述，这些结果为海马胆碱能机制在短日照引起的季节性抑郁情绪状态中的作用提供了证据。
Seasonal variations in environmental light influence switches between moods in seasonal affective disorder (SAD) and bipolar disorder (BD), with depression arising during short active (SA) winter periods. Light-induced changes behavior are also seen in healthy animals and are intensified in mice with reduced dopamine transporter expression. Specifically, decreasing the nocturnal active period (SA) of mice increases punishment perseveration and forced swim test (FST) immobility. Elevating acetylcholine with the acetylcholinesterase inhibitor physostigmine induces depression symptoms in people and increases FST immobility in mice. We utilized SA photoperiods and physostigmine to elevate acetylcholine prior to testing in a probabilistic learning task and the FST, including reversing subsequent deficits with nicotinic and scopolamine antagonists and targeted hippocampal adeno-associated viral administration. We confirmed that physostigmine also increases punishment sensitivity in a probabilistic learning paradigm. In addition, muscarinic and nicotinic receptor blockade attenuated both physostigmine- and SA-induced phenotypes. Finally, viral-mediated hippocampal expression of human AChE used to lower ACh levels blocked SA-induced elevation of FST immobility. These results indicate that increased hippocampal acetylcholine neurotransmission is necessary for the expression of SA exposure-induced behaviors. Furthermore, these studies support the potential for cholinergic treatments in depression. Taken together, these results provide evidence for hippocampal cholinergic mechanisms in contributing to seasonally-depressed affective states induced by short day lengths.
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影响因子：
4.7
作者：
Milienne-Petiot M;Kesby JP;Graves M;van Enkhuizen J;Semenova S;Minassian A;Markou A;Geyer MA;Young JW
通讯作者：
Young JW
影响因子：
56.9
作者：
Dulcis, Davide;Jamshidi, Pouya;Spitzer, Nicholas C.
通讯作者：
Spitzer, Nicholas C.
影响因子：
10.6
作者：
Caldarone, BJ;Harrist, A;Picciotto, MR
通讯作者：
Picciotto, MR
影响因子：
3.8
作者：
Must A;Horvath S;Nemeth VL;Janka Z
通讯作者：
Janka Z
影响因子：
10.6
作者：
Adida, Marc;Jollant, Fabrice;Courtet, Philippe
通讯作者：
Courtet, Philippe