Regulation of depression-related behaviors by GABAergic neurons in the lateral septum through periaqueductal gray neuronal projections
| Autor: | Dan Wang, Chen Li, Di Zhao, Minghu Cui, Jing Liu, Shujun Jiang, Fengai Hu, Fantao Meng, Haifeng Lian, Jingjing You, Dunjiang Liu, He Ma, Cuilan Liu, Wentao Wang |
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| Rok vydání: | 2021 |
| Předmět: |
Biology
Periaqueductal gray 03 medical and health sciences 0302 clinical medicine Sniffing Neural Pathways medicine Humans Periaqueductal Gray Premovement neuronal activity Chronic stress GABAergic Neurons Biological Psychiatry Depressive Disorder Major Depression medicine.disease Antidepressive Agents 030227 psychiatry Psychiatry and Mental health nervous system Antidepressant GABAergic Major depressive disorder Female Neuroscience 030217 neurology & neurosurgery Behavioural despair test |
| Zdroj: | Journal of Psychiatric Research. 137:202-214 |
| ISSN: | 0022-3956 |
| Popis: | Major depressive disorder (MDD) is a serious and widespread mental illness worldwide. The abnormality of neuronal networks may contribute to the etiology of MDD. However, the neural connections underlying the main symptoms of MDD need further elucidation. Here, we found that GABAergic neurons in the lateral septum (LS) were activated by chronic unpredictable stress (CUS), with increased numbers of ΔFosB-labeled neurons. LS neuronal activity was modulated using a chemogenetic approach. Activation of LS neurons caused a depressive phenotype, as shown by increased immobility in the forced swim test, and induced increased susceptibility to subthreshold chronic stress, as indicated by decreased female urine sniffing time and preference for sucrose in depression-related behavior detection, whereas suppression of LS neuronal activity induced an antidepressant effect under basal and stressed conditions. Moreover, we found that the LS showed strong neuronal projections to the dorsal periaqueductal gray (dPAG); activation of dPAG-projecting GABAergic neurons in the LS produced the same depressive behaviors and stress susceptibility as induced by the activation of the majority of LS GABAergic neurons. Finally, we found that activation of neuronal fibers in the dPAG derived from the LS showed depression-related behaviors, as suggested by the decreased female urine sniffing time and sucrose preference in female urine sniffing and sucrose preference tests respectively. Our findings indicate that LS is a key depression-controlling nucleus, and that the LS-PAG projection is an essential effector circuit for morbidity and treatment in depression. |
| Databáze: | OpenAIRE |
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