Rationale

Major depression is a serious, but common, psychological disorder, which consists of a long-lasting depressive mood, feelings of helplessness, anhedonia, and sleep disturbances. It has been reported that rats with bilateral olfactory bulbectomies (OBXs) exhibit depressive-like behaviors which indicates that the olfactory bulb (OB) plays an important role in the formation of depression. However, which type of OB neurons plays an important role in the formation of depression remains unclear.

Objective

To determine the role of OB neuronal types in depression and related sleep-wake dysfunction.

Methods

Firstly, we established and evaluated a conventional physical bilateral OBX depression model. Secondly, we used chemical methods to ablate OB neurons, while maintaining the original shape, and evaluated depressive-like behaviors. Thirdly, we utilized AAV-flex-taCasp3-TEVp and transgenetic mice to specifically ablate the OB GABAergic or glutamatergic neurons, then evaluated depressive-like behaviors.

Results

Compared with measured parameters in sham mice, mice with OBXs or ibotenic acid–induced OB lesions exhibited depressive-like behaviors and sleep disturbances, as demonstrated by results of depressive-like behavior tests and sleep recordings. Selective lesioning of OB glutamatergic neurons, but not GABAergic neurons induced depressive-like behaviors and increased rapid eye movement sleep during the light phase of the circadian cycle.

Conclusions

These results indicate that OB glutamatergic neurons play a key role in olfactory-related depression and sleep disturbance.

中文翻译：

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嗅球谷氨酸能神经元的消融诱导小鼠抑郁样行为和睡眠障碍。

基本原理

重度抑郁症是一种严重但常见的心理疾病，包括长期的抑郁情绪，无助感，快感不足和睡眠障碍。据报道，患有双侧嗅球囊切除术（OBX）的大鼠表现出抑郁样行为，这表明嗅球（OB）在抑郁症的形成中起重要作用。但是，哪种类型的OB神经元在抑郁症的形成中起着重要作用尚不清楚。

目的

确定OB神经元类型在抑郁症和相关的睡眠-觉醒功能障碍中的作用。

方法

首先，我们建立并评估了常规的物理双侧OBX抑郁症模型。其次，我们使用化学方法消融OB神经元，同时保持其原始形状，并评估了抑郁样行为。第三，我们利用AAV-flex-taCasp3-TEVp和转基因小鼠专门消融OB GABA能或谷氨酸能神经元，然后评估抑郁样行为。

结果

与假手术小鼠的测量参数相比，患有OBX或异丁酸的OB病变的小鼠表现出抑郁样行为和睡眠障碍，如抑郁样行为测试和睡眠记录的结果所示。在昼夜节律周期的轻度阶段，OB谷氨酸能神经元（而不是GABA能神经元）的选择性损伤会诱发抑郁样行为并增加快速眼动睡眠。

结论

这些结果表明，OB谷氨酸能神经元在嗅觉相关性抑郁症和睡眠障碍中起关键作用。