Article
Multidisciplinary Sciences
Linda D. Simmler, Yue Li, Lotfi C. Hadjas, Agnes Hiver, Ruud van Zessen, Christian Luscher
Summary: Ketamine does not induce synaptic plasticity in the nucleus accumbens despite eliciting dopamine transients, due to the rapid off-kinetics of the dopamine transients and NMDAR antagonism. However, it supports reinforcement through NMDAR antagonism in GABA neurons of the ventral tegmental area, which is quickly terminated by type-2 dopamine receptors on dopamine neurons.
Review
Biochemistry & Molecular Biology
Sari Goldstein Ferber, Aron Weller, Gal Yadid, Alexander Friedman
Summary: Depression is the most common psychiatric disorder in the Western world, characterized by increased negative affect and decreased positive affect, with some types having a risk for suicide attempts. Recent studies suggest a relationship between alterations in dopaminergic activity and depression, with imaging studies revealing decreased activity in brain reward circuits in major depression. This review explores the crosstalk between endocannabinoid and dopamine receptors in reward circuits and their vulnerability to stress, particularly in corticostriatal regions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Anesthesiology
Wenjie Ren, Maria Virginia Centeno, Xuhong Wei, Ian Wickersham, Marco Martina, A. Vania Apkarian, D. James Surmeier
Summary: The nucleus accumbens and the ventral tegmental area play crucial roles in shaping chronic pain states by altering functional connectivity and dopamine signaling. Adaptive changes induced by SNI in these regions can alleviate anxiety and social withdrawal, but countervailing mechanisms may contribute to the chronic pain state.
Article
Biochemistry & Molecular Biology
Olga Skiteva, Ning Yao, Giacomo Sitzia, Karima Chergui
Summary: This study reveals alterations in glutamatergic synaptic transmission in DA neurons of the SNc and VTA before the onset of motor impairments in the LRRK2-G2019S mouse model of PD.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Changyou Jiang, Xiao Yang, Guanhong He, Fan Wang, Zhilin Wang, Wendong Xu, Ying Mao, Lan Ma, Feifei Wang
Summary: Neuronal plasticity in the ventral tegmental area (VTA) is crucial for drug dependence, with morphine exposure leading to preferential projection of neurons to the nucleus accumbens (NAc) and dopamine-dependent positive reinforcement. Chronic morphine exposure enhances connections between corticotrophin-releasing hormone (CRH) neurons of the central amygdala and VTA neurons, mediating negative effects during opiate withdrawal. Pharmacological intervention or CRISPR-mediated repression of CRH receptors weakens inhibitory inputs and alleviates negative effects during opiate withdrawal.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
E. Liu, Kunkun Pang, Min Liu, Xu Tan, Zhaofang Hang, Shouhong Mu, Weikai Han, Qingwei Yue, Stefano Comai, Jinhao Sun
Summary: The brain circuit between the ventral tegmental area (VTA) and nucleus accumbens lateral shell (NAcLat) plays a crucial role in methamphetamine addiction. By isolating and profiling dopamine (DA) neurons in the VTA-NAcLat circuit of MA-treated mice, researchers discovered that downregulation of KCNQ genes, encoding Kv7 channel proteins, was associated with addiction. Activation of Kv7.2/3 and Kv7.4 channels attenuated MA-induced addiction behaviors by reducing neuronal excitability and dopamine release.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Daniel J. Kalamarides, Aditi Singh, Shannon L. Wolfman, John A. Dani
Summary: The effectiveness of current treatments for opioid use disorder varies by sex, and there is a lack of understanding about the neurobiological mechanisms mediating negative states during withdrawal, particularly in terms of sex differences. Preclinical research in male subjects suggests that opioid withdrawal is accompanied by increased GABA release probability in the VTA. However, it is uncertain if these findings extend to females. In this study, it was found that inhibitory synaptic long-term potentiation is occluded in the VTA in male mice after repeated morphine injections and withdrawal, while female mice maintain the ability to evoke synaptic potentiation.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Shuangshuang Ma, Min Chen, Yihao Jiang, Xinkuan Xiang, Shiqi Wang, Zuohang Wu, Shuo Li, Yihui Cui, Junying Wang, Yanqing Zhu, Yan Zhang, Huan Ma, Shumin Duan, Haohong Li, Yan Yang, Christopher J. Lingle, Hailan Hu
Summary: By manipulating the interactions between the lateral habenula (LHb) and NMDARs, we are able to adjust the duration of ketamine's antidepressant effects in vivo. This study reveals the causal mechanisms behind the sustained antidepressant effects of ketamine and opens up new possibilities for therapeutic use.
Article
Multidisciplinary Sciences
Shuangshuang Ma, Min Chen, Yihao Jiang, Xinkuan Xiang, Shiqi Wang, Zuohang Wu, Shuo Li, Yihui Cui, Junying Wang, Yanqing Zhu, Yan Yang, Huan Ma, Shumin Duan, Haohong Li, Yan Yang, Christopher J. Lingle, Hailan Hu
Summary: Ketamine, a potent antidepressant, continues to suppress neuronal firing and block NMDARs in the brain for up to 24 hours after a single injection. This sustained effect is not due to endocytosis, but rather the trapping of ketamine in NMDARs. By modulating the activity of NMDARs, the duration of ketamine action can be controlled, providing new opportunities for therapeutic use of ketamine.
Article
Neurosciences
Ping Cai, Hui-Yun Chen, Wei-Tao Tang, Yu-Duan Hu, Shang-Yi Chen, Jing-Shan Lu, Zhi-Hui Lin, Sheng-Nan Huang, Li-Huan Hu, Wei-Kun Su, Qi-Xuan Li, Zhi-Jie Lin, Tian-Rui Kang, Xiong-Bin Yan, Pei-Chang Liu, Li Chen, Dou Yin, Si-Ying Wu, Huang-Yuan Li, Changxi Yu
Summary: Defensive behavior is essential for animal survival in the natural environment, and a high arousal state and immediate sleep-to-wakefulness transition are required for successful defensive measures. Research has shown that the glutamatergic basal forebrain plays a role in sleep-wake regulation and encodes defensive behaviors through the glutamatergic BF-VTA pathway. Overexcitation of this pathway may be implicated in psychiatric disorders characterized by exaggerated defensive responses.
Article
Multidisciplinary Sciences
Marta E. Soden, Joshua X. Yee, Larry S. Zweifel
Summary: This study reveals that fast-acting neurotransmitters and slow, modulatory neuropeptides can co-regulate neural circuit outputs through different signaling pathways. By using a genetic-based anatomical disconnect procedure, researchers were able to independently edit neurotransmitter- and neuropeptide-related genes in specific cell types. It was found that the neurotransmitter GABA and the neuropeptide neurotensin work together to regulate dopamine neuron responses and optimize behavior.
Article
Neurosciences
Gemma Navarro, William Rea, Cesar Quiroz, Estefania Moreno, Devan Gomez, Cody J. Wenthur, Vicent Casado, Lorenzo Leggio, Matthew C. Hearing, Sergi Ferre
Summary: GHS-R1b facilitates oligomerization with GHS-R1a, impacting its pharmacological properties, but GHSR1a:GHS-R1b:D1R oligomers in the VTA are the main mediators of the dopaminergic effects of ghrelin.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Cell Biology
Guilian Tian, May Hui, Desiree Macchia, Pieter Derdeyn, Alexandra Rogers, Elizabeth Hubbard, Chengfeng Liu, Jose J. Vasquez, Lara Taniguchi, Katrina Bartas, Sean Carroll, Kevin T. Beier
Summary: This study reveals the selective role of ventral tegmental area dopamine projection to the amygdala in cocaine-induced anxiety. The activity of inhibitory GABAergic cells and downstream dopamine cells in the bed nucleus of the stria terminalis and amygdala is elevated even after a single cocaine exposure. Silencing this projection prevents the development of anxiety during protracted withdrawal after cocaine administration. Furthermore, the activation of dopamine cells in the amygdala is necessary and sufficient for reinstatement of cocaine place preference.
Article
Neurosciences
Lianwei Mu, Xiaojie Liu, Hao Yu, Mengming Hu, Vladislav Friedman, Thomas J. Kelly, Li Zhao, Qing-song Liu
Summary: Ibudilast effectively reduces the reinforcing effects of cocaine and relapse to cocaine seeking behavior. This may be achieved by restoring the balance between excitation and inhibition in VTA dopamine neurons.
Article
Neurosciences
Teresa M. Nufer, Bridget J. Wu, Zachary Boyce, Scott C. Steffensen, Jeffrey G. Edwards
Summary: The ventral tegmental area (VTA) is a crucial part of the mesocorticolimbic dopamine (DA) circuit involved in reward and motivated behaviors. This area contains DA neurons and GABAergic inhibitory cells that regulate DA cell activity. The plasticity of inhibitory inputs to VTA GABA neurons, specifically in response to drug exposure, is not well understood.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Neurosciences
Daniel Jenson, Kechun Yang, Alexandra Acevedo-Rodriguez, Amber Levine, John I. Broussard, Jianrong Tang, John A. Dani
Article
Cell Biology
John I. Broussard, Kechun Yang, Amber T. Levine, Theodoros Tsetsenis, Daniel Jenson, Fei Cao, Isabella Garcia, Benjamin R. Arenkiel, Fu-Ming Zhou, Mariella De Biasi, John A. Dani
Article
Clinical Neurology
Guohui Li, Kechun Yang, Chao Zheng, Qiang Liu, Yongchang Chang, John F. Kerrigan, Jie Wu
ANNALS OF NEUROLOGY
(2011)
Review
Neurosciences
Brian W. Leonard, Diego Mastroeni, Andrew Grover, Qiang Liu, Kechun Yang, Ming Gao, Jie Wu, David Pootrakul, Simone A. Van den Berge, Elly M. Hol, Joseph Rogers
JOURNAL OF COMPARATIVE NEUROLOGY
(2009)
Article
Neurosciences
Kechun Yang, Lori Buhlman, Ghous M. Khan, Robert A. Nichols, Guozhang Jin, J. Michael McIntosh, Paul Whiteaker, Ronald J. Lukas, Jie Wu
JOURNAL OF NEUROSCIENCE
(2011)
Article
Pharmacology & Pharmacy
Chao Zheng, Kechun Yang, Qiang Liu, Meng-Ya Wang, Jianxin Shen, A. Sofia Valles, Ronald J. Lukas, Francisco J. Barrantes, Jie Wu
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2010)
Article
Neurosciences
Chen Wu, Kechun Yang, Qiang Liu, Matoko Wakui, Guo-Zhang Jin, Xuechu Zhen, Jie Wu
Article
Neurosciences
Yu Jin, Kechun Yang, Hong Wang, Jie Wu
Article
Cell Biology
Kechun Yang, Yun Xue, Xiaoya Gao
Summary: XIST levels were found to be elevated in the serum of AS patients and ox-LDL-treated AS cell models. XIST depletion restrained cell proliferation and induced apoptosis in AS cell models, while miR-599 was identified as a direct downstream target of XIST reversing the effects of XIST knockdown on AS progression. XIST was also shown to increase TLR4 expression by serving as a ceRNA of miR-599, implicating the XIST/miR-599/TLR4 axis in AS development.
Article
Medicine, Research & Experimental
Xiaoya Gao, Yun Xue, Kechun Yang
Summary: The study demonstrated that LINC00899 could enhance osteogenic differentiation of hBMSCs and prevent osteoporosis by sponging miR-374a to enhance the expression of RUNX2. This provides a potentially useful therapeutic strategy for patients with osteoporosis.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Multidisciplinary Sciences
Theodoros Tsetsenis, Julia K. Badyna, Julianne A. Wilson, Xiaowen Zhang, Elizabeth N. Krizman, Manivannan Subramaniyan, Kechun Yang, Steven A. Thomas, John A. Dani
Summary: This study identifies a cluster of midbrain dopamine neurons near the hippocampus that send direct projections and play a crucial role in aversive memory formation. The neuromodulation of midbrain dopamine in the hippocampus is sufficient to maintain aversive memory formation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Julia K. Brynildsen, Kechun Yang, Crystal Lemchi, John A. Dani, Mariella De Biasi, Julie A. Blendy
Summary: The SNP D398N in the CHRNA5 gene has been associated with nicotine and opiate dependence. By using CRISPR/Cas9 genome editing, mice with the risk-associated allele were generated and it was found that this genotype may enhance opioid reward specifically in females. The response of DA neurons to morphine was altered in Chrna5 A/A mice, and increased opiate reward was observed two weeks after conditioning.
Article
Endocrinology & Metabolism
Guangjin Yong, Qian Jing, Qing Yao, Kechun Yang, Xinhua Ye
Summary: Studies suggest that consuming carbohydrates last during meals can lower postprandial glucose excursions more effectively than consuming carbohydrates first. However, this phenomenon has not been studied in gestational diabetes mellitus (GDM). This study found that changing meal sequences or increasing the number of meals may reduce glycemic excursions in GDM.
JOURNAL OF DIABETES RESEARCH
(2022)
Article
Neurosciences
Kechun Yang, Ian McLaughlin, Jessica K. Shaw, Natalia Quijano-Cardre, John A. Dani, Mariella De Biasi
Summary: Nicotine, the active component in tobacco, acts on neuronal nicotinic acetylcholine receptors (nAChR) to cause addiction. The CHRNA5 gene, which encodes the a5 subunit of nAChR, is associated with nicotine use and dependence. Studies on rodents have shown that a5-containing nAChRs in dopamine neurons in the ventral tegmental area (VTA) play a significant role in nicotine reward and reinforcement. However, the specific contributions of a5-containing nAChRs to the cellular adaptations associated with long-term nicotine exposure are still unknown. To investigate this, researchers conducted electrophysiological experiments on VTA neurons and found that CHRNA5 mutation led to profound changes in nAChR function during chronic nicotine exposure and withdrawal. The results highlight the importance of VTA a5-nAChRs in the response to nicotine and suggest their involvement in the withdrawal process.