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 in 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 used 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-induced 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.

环境光影响的季节性变化在季节性情感障碍 (SAD) 和双相情感障碍 (BD) 的情绪之间切换，抑郁症出现在短暂的活跃 (SA) 冬季期间。在健康动物中也观察到光诱导的行为变化，并且在多巴胺转运蛋白表达降低的小鼠中加剧。具体来说，减少小鼠的夜间活动期 (SA) 会增加惩罚坚持和强迫游泳测试 (FST) 不动。用乙酰胆碱酯酶抑制剂毒扁豆碱升高乙酰胆碱会诱发人的抑郁症状并增加小鼠的 FST 不动。在概率学习任务和 FST 测试之前，我们使用 SA 光周期和毒扁豆碱来提高乙酰胆碱，包括用烟碱和东莨菪碱拮抗剂逆转随后的缺陷以及靶向海马腺相关病毒给药。我们证实毒扁豆碱还增加了概率学习范式中的惩罚敏感性。此外，毒蕈碱和烟碱受体阻断减弱毒扁豆碱诱导和 SA 诱导的表型。最后，用于降低 ACh 水平的病毒介导的人类 AChE 海马表达阻止了 SA 诱导的 FST 不动性升高。这些结果表明，增加海马乙酰胆碱神经传递对于 SA 暴露诱导行为的表达是必要的。此外，这些研究支持胆碱能治疗抑郁症的潜力。综合起来，