Reactivating a positive feedback loop VTA-BLA-NAc circuit associated with positive experience ameliorates the attenuated reward sensitivity induced by chronic stress
Both genetic predisposition and life events, particularly life stress, are thought to increase the risk for depression. Reward sensitivity appears to be attenuated in major depressive disorder (MDD), suggesting deficits in reward processing in these patients. We identified the VTA-BLA-NAc circuit as...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-11-01
|
| Series: | Neurobiology of Stress |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289521000783 |
| _version_ | 1819101425784848384 |
|---|---|
| author | Linshan Sun Jingjing You Fengjiao Sun Minghu Cui Jiangong Wang Wentao Wang Dan Wang Dunjiang Liu Zhicheng Xu Changyun Qiu Bin Liu Haijing Yan |
| author_facet | Linshan Sun Jingjing You Fengjiao Sun Minghu Cui Jiangong Wang Wentao Wang Dan Wang Dunjiang Liu Zhicheng Xu Changyun Qiu Bin Liu Haijing Yan |
| author_sort | Linshan Sun |
| collection | DOAJ |
| description | Both genetic predisposition and life events, particularly life stress, are thought to increase the risk for depression. Reward sensitivity appears to be attenuated in major depressive disorder (MDD), suggesting deficits in reward processing in these patients. We identified the VTA-BLA-NAc circuit as being activated by sex reward, and the VTA neurons that respond to sex reward are mostly dopaminergic. Acute or chronic reactivation of this circuit ameliorates the reward insensitivity induced by chronic restraint stress. Our histological and electrophysiological results show that the VTA neuron subpopulation responding to restraint stress, predominantly GABAergic neurons, inhibits the responsiveness of VTA dopaminergic neurons to reward stimuli, which is probably the mechanism by which stress modulates the reward processing neural circuits and subsequently disrupts reward-related behaviours. Furthermore, we found that the VTA-BLA-NAc circuit is a positive feedback loop. Blocking the projections from the BLA to the NAc associated with sex reward increases the excitability of VTA GABAergic neurons and decreases the excitability of VTA dopaminergic neurons, while activating this pathway decreases the excitability of VTA GABAergic neurons and increases the excitability of VTA dopaminergic neurons, which may be the cellular mechanism by which the VTA-BLA-NAc circuit associated with sex reward ameliorates the attenuated reward sensitivity induced by chronic stress. |
| first_indexed | 2024-12-22T01:18:28Z |
| format | Article |
| id | doaj.art-eb29f62e6e9b4950a46e919b4f6c9d27 |
| institution | Directory Open Access Journal |
| issn | 2352-2895 |
| language | English |
| last_indexed | 2024-12-22T01:18:28Z |
| publishDate | 2021-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Stress |
| spelling | doaj.art-eb29f62e6e9b4950a46e919b4f6c9d272022-12-21T18:43:48ZengElsevierNeurobiology of Stress2352-28952021-11-0115100370Reactivating a positive feedback loop VTA-BLA-NAc circuit associated with positive experience ameliorates the attenuated reward sensitivity induced by chronic stressLinshan Sun0Jingjing You1Fengjiao Sun2Minghu Cui3Jiangong Wang4Wentao Wang5Dan Wang6Dunjiang Liu7Zhicheng Xu8Changyun Qiu9Bin Liu10Haijing Yan11Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, China; Department of Neurology, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, ChinaInstitute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, ChinaInstitute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, ChinaDepartment of Psychiatry, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, ChinaInstitute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, ChinaInstitute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, ChinaInstitute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, ChinaInstitute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, ChinaInstitute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, ChinaInstitute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, ChinaInstitute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, China; Corresponding author.Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, China; Department of Pharmacology, College of Basic Medicine, Binzhou Medical University, 264003, Yantai, Shandong, China; Corresponding author. Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, 256603, Binzhou, Shandong, China.Both genetic predisposition and life events, particularly life stress, are thought to increase the risk for depression. Reward sensitivity appears to be attenuated in major depressive disorder (MDD), suggesting deficits in reward processing in these patients. We identified the VTA-BLA-NAc circuit as being activated by sex reward, and the VTA neurons that respond to sex reward are mostly dopaminergic. Acute or chronic reactivation of this circuit ameliorates the reward insensitivity induced by chronic restraint stress. Our histological and electrophysiological results show that the VTA neuron subpopulation responding to restraint stress, predominantly GABAergic neurons, inhibits the responsiveness of VTA dopaminergic neurons to reward stimuli, which is probably the mechanism by which stress modulates the reward processing neural circuits and subsequently disrupts reward-related behaviours. Furthermore, we found that the VTA-BLA-NAc circuit is a positive feedback loop. Blocking the projections from the BLA to the NAc associated with sex reward increases the excitability of VTA GABAergic neurons and decreases the excitability of VTA dopaminergic neurons, while activating this pathway decreases the excitability of VTA GABAergic neurons and increases the excitability of VTA dopaminergic neurons, which may be the cellular mechanism by which the VTA-BLA-NAc circuit associated with sex reward ameliorates the attenuated reward sensitivity induced by chronic stress.http://www.sciencedirect.com/science/article/pii/S2352289521000783Reward insensitivityChronic stressVTA-BLA-NAc circuitPositive feedback loop |
| spellingShingle | Linshan Sun Jingjing You Fengjiao Sun Minghu Cui Jiangong Wang Wentao Wang Dan Wang Dunjiang Liu Zhicheng Xu Changyun Qiu Bin Liu Haijing Yan Reactivating a positive feedback loop VTA-BLA-NAc circuit associated with positive experience ameliorates the attenuated reward sensitivity induced by chronic stress Neurobiology of Stress Reward insensitivity Chronic stress VTA-BLA-NAc circuit Positive feedback loop |
| title | Reactivating a positive feedback loop VTA-BLA-NAc circuit associated with positive experience ameliorates the attenuated reward sensitivity induced by chronic stress |
| title_full | Reactivating a positive feedback loop VTA-BLA-NAc circuit associated with positive experience ameliorates the attenuated reward sensitivity induced by chronic stress |
| title_fullStr | Reactivating a positive feedback loop VTA-BLA-NAc circuit associated with positive experience ameliorates the attenuated reward sensitivity induced by chronic stress |
| title_full_unstemmed | Reactivating a positive feedback loop VTA-BLA-NAc circuit associated with positive experience ameliorates the attenuated reward sensitivity induced by chronic stress |
| title_short | Reactivating a positive feedback loop VTA-BLA-NAc circuit associated with positive experience ameliorates the attenuated reward sensitivity induced by chronic stress |
| title_sort | reactivating a positive feedback loop vta bla nac circuit associated with positive experience ameliorates the attenuated reward sensitivity induced by chronic stress |
| topic | Reward insensitivity Chronic stress VTA-BLA-NAc circuit Positive feedback loop |
| url | http://www.sciencedirect.com/science/article/pii/S2352289521000783 |
| work_keys_str_mv | AT linshansun reactivatingapositivefeedbackloopvtablanaccircuitassociatedwithpositiveexperienceamelioratestheattenuatedrewardsensitivityinducedbychronicstress AT jingjingyou reactivatingapositivefeedbackloopvtablanaccircuitassociatedwithpositiveexperienceamelioratestheattenuatedrewardsensitivityinducedbychronicstress AT fengjiaosun reactivatingapositivefeedbackloopvtablanaccircuitassociatedwithpositiveexperienceamelioratestheattenuatedrewardsensitivityinducedbychronicstress AT minghucui reactivatingapositivefeedbackloopvtablanaccircuitassociatedwithpositiveexperienceamelioratestheattenuatedrewardsensitivityinducedbychronicstress AT jiangongwang reactivatingapositivefeedbackloopvtablanaccircuitassociatedwithpositiveexperienceamelioratestheattenuatedrewardsensitivityinducedbychronicstress AT wentaowang reactivatingapositivefeedbackloopvtablanaccircuitassociatedwithpositiveexperienceamelioratestheattenuatedrewardsensitivityinducedbychronicstress AT danwang reactivatingapositivefeedbackloopvtablanaccircuitassociatedwithpositiveexperienceamelioratestheattenuatedrewardsensitivityinducedbychronicstress AT dunjiangliu reactivatingapositivefeedbackloopvtablanaccircuitassociatedwithpositiveexperienceamelioratestheattenuatedrewardsensitivityinducedbychronicstress AT zhichengxu reactivatingapositivefeedbackloopvtablanaccircuitassociatedwithpositiveexperienceamelioratestheattenuatedrewardsensitivityinducedbychronicstress AT changyunqiu reactivatingapositivefeedbackloopvtablanaccircuitassociatedwithpositiveexperienceamelioratestheattenuatedrewardsensitivityinducedbychronicstress AT binliu reactivatingapositivefeedbackloopvtablanaccircuitassociatedwithpositiveexperienceamelioratestheattenuatedrewardsensitivityinducedbychronicstress AT haijingyan reactivatingapositivefeedbackloopvtablanaccircuitassociatedwithpositiveexperienceamelioratestheattenuatedrewardsensitivityinducedbychronicstress |