scholarly journals Distinct Alterations in Cerebellar Connectivity with Substantia Nigra and Ventral Tegmental Area in Parkinsons Disease

2021 ◽  
Author(s):  
Ian M O'Shea ◽  
Haroon Popal ◽  
Ingrid R Olson ◽  
Vishnu P Murty ◽  
David V Smith
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Occipital Cortex ◽  
Resting State Fmri ◽  
Healthy Adults ◽  
Anterior Cingulate ◽  
Functional Coupling ◽  
Parkinsons Disease ◽  
Ventral Tegmental

In Parkinsons disease (PD), neurodegeneration of dopaminergic neurons occurs in the midbrain, specifically targeting the substantia nigra (SN), while leaving the ventral tegmental area (VTA) relatively spared in early phases of the disease. Although the SN and VTA are known to be functionally dissociable in healthy adults, it remains unclear how this dissociation is altered in PD. To examine this issue, we performed a whole-brain analysis to compare functional coupling in PD to healthy adults using resting-state fMRI data compiled from three independent datasets. Our analysis showed that across the sample, the SN had greater coupling to the precuneus, anterior cingulate gyrus, and areas of the occipital cortex, partially replicating our previous work in healthy young adults. Notably, we also found that, in PD, VTA-right cerebellum coupling was higher than SN-right cerebellum coupling, whereas the opposite trend occurred in healthy controls. This double dissociation may reflect a compensatory role of the cerebellum in PD and could provide a potential target for future study and treatment.

scholarly journals Genetic inactivation of alpha-synuclein affects embryonic development of dopaminergic neurons of the substantia nigra, but not the ventral tegmental area, in mouse brain

2018 ◽  
Author(s):  
Tatiana V Tarasova ◽  
Olga A Lytkina ◽  
Valeria V Goloborshcheva ◽  
Larisa N Skuratovskaya ◽  
Alexandr I Antohin ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Embryonic Development ◽  
Ventral Tegmental Area ◽  
Knockout Mice ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Nigrostriatal System ◽  
Ventral Tegmental

Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson's disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration. Here we have studied the dynamics of changes in TH-positive cell numbers in the SN and VTA during a critical period of their embryonic development in alpha-synuclein knockout mice. This precise study of DA neurons during development of the SN revealed that not only is the number of DA neurons reduced by the end of the period of ontogenic selection, but that the way these neurons are formed is altered in alpha-synuclein knockout mice. At the same time, DA neurons in the VTA are not affected. Alpha-synuclein exerts a modulating effect on the formation of DA neurons in the SN and has no effect on the formation of DA neurons in VTA, the structure that is much less susceptible to degeneration in PD brain, suggesting a potential role of alpha-synuclein in the development of the population of DA neurons in substantia nigra.

scholarly journals Genetic inactivation of alpha-synuclein affects embryonic development of dopaminergic neurons of the substantia nigra, but not the ventral tegmental area, in mouse brain

2018 ◽  
Author(s):  
Tatiana V Tarasova ◽  
Olga A Lytkina ◽  
Valeria V Goloborshcheva ◽  
Larisa N Skuratovskaya ◽  
Alexandr I Antohin ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Embryonic Development ◽  
Ventral Tegmental Area ◽  
Knockout Mice ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Nigrostriatal System ◽  
Ventral Tegmental

Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson's disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration. Here we have studied the dynamics of changes in TH-positive cell numbers in the SN and VTA during a critical period of their embryonic development in alpha-synuclein knockout mice. This precise study of DA neurons during development of the SN revealed that not only is the number of DA neurons reduced by the end of the period of ontogenic selection, but that the way these neurons are formed is altered in alpha-synuclein knockout mice. At the same time, DA neurons in the VTA are not affected. Alpha-synuclein exerts a modulating effect on the formation of DA neurons in the SN and has no effect on the formation of DA neurons in VTA, the structure that is much less susceptible to degeneration in PD brain, suggesting a potential role of alpha-synuclein in the development of the population of DA neurons in substantia nigra.

scholarly journals Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular Axons

2021 ◽  
Vol 9 ◽  
Author(s):  
Verónica Company ◽  
Abraham Andreu-Cervera ◽  
M. Pilar Madrigal ◽  
Belén Andrés ◽  
Francisca Almagro-García ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Dopaminergic Neurons ◽  
Functional Organization ◽  
Substantia Nigra Pars Compacta ◽  
Fasciculus Retroflexus ◽  
Ventral Tegmental

The fasciculus retroflexus is an important fascicle that mediates reward-related behaviors and is associated with different psychiatric diseases. It is the main habenular efference and constitutes a link between forebrain regions, the midbrain, and the rostral hindbrain. The proper functional organization of habenular circuitry requires complex molecular programs to control the wiring of the habenula during development. However, the mechanisms guiding the habenular axons toward their targets remain mostly unknown. Here, we demonstrate the role of the mesodiencephalic dopaminergic neurons (substantia nigra pars compacta and ventral tegmental area) as an intermediate target for the correct medial habenular axons navigation along the anteroposterior axis. These neuronal populations are distributed along the anteroposterior trajectory of these axons in the mesodiencephalic basal plate. Using in vitro and in vivo experiments, we determined that this navigation is the result of netrin 1 attraction generated by the mesodiencephalic dopaminergic neurons. This attraction is mediated by the receptor deleted in colorectal cancer (DCC), which is strongly expressed in the medial habenular axons. The increment in our knowledge on the fasciculus retroflexus trajectory guidance mechanisms opens the possibility of analyzing if its alteration in mental health patients could account for some of their symptoms.

scholarly journals Leptin Receptor Expressing Neurons in the Substantia Nigra Regulate Locomotion, and in The Ventral Tegmental Area Motivation and Feeding

2021 ◽  
Vol 12 ◽  
Author(s):  
Véronne A. J. de Vrind ◽  
Lisanne J. van ‘t Sant ◽  
Annemieke Rozeboom ◽  
Mieneke C. M. Luijendijk-Berg ◽  
Azar Omrani ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Food Reward ◽  
Leptin Receptor ◽  
Ventral Tegmental ◽  
Motivational Behavior ◽  
Lepr Expression

Leptin is an anorexigenic hormone, important in the regulation of body weight. Leptin plays a role in food reward, feeding, locomotion and anxiety. Leptin receptors (LepR) are expressed in many brain areas, including the midbrain. In most studies that target the midbrain, either all LepR neurons of the midbrain or those of the ventral tegmental area (VTA) were targeted, but the role of substantia nigra (SN) LepR neurons has not been investigated. These studies have reported contradicting results regarding motivational behavior for food reward, feeding and locomotion. Since not all midbrain LepR mediated behaviors can be explained by LepR neurons in the VTA alone, we hypothesized that SN LepR neurons may provide further insight. We first characterized SN LepR and VTA LepR expression, which revealed LepR expression mainly on DA neurons. To further understand the role of midbrain LepR neurons in body weight regulation, we chemogenetically activated VTA LepR or SN LepR neurons in LepR-cre mice and tested for motivational behavior, feeding and locomotion. Activation of VTA LepR neurons in food restricted mice decreased motivation for food reward (p=0.032) and food intake (p=0.020), but not locomotion. In contrast, activation of SN LepR neurons in food restricted mice decreased locomotion (p=0.025), but not motivation for food reward or food intake. Our results provide evidence that VTA LepR and SN LepR neurons serve different functions, i.e. activation of VTA LepR neurons modulated motivation for food reward and feeding, while SN LepR neurons modulated locomotor activity.

The role of alpha-synuclein in the development of the dopaminergic neurons in the substantia nigra and ventral tegmental area

2016 ◽  
Vol 466 (1) ◽  
pp. 5-7 ◽  
Author(s):  
T. V. Tarasova ◽  
O. A. Lytkina ◽  
A. Yu. Roman ◽  
S. O. Bachurin ◽  
A. A. Ustyugov
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Dopaminergic Neurons ◽  
Alpha Synuclein ◽  
Ventral Tegmental

scholarly journals Genetic inactivation of alpha-synuclein affects embryonic development of dopaminergic neurons of the substantia nigra, but not the ventral tegmental area, in mouse brain

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4779 ◽  
Author(s):  
Tatiana V. Tarasova ◽  
Olga A. Lytkina ◽  
Valeria V. Goloborshcheva ◽  
Larisa N. Skuratovskaya ◽  
Alexandr I. Antohin ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Embryonic Development ◽  
Ventral Tegmental Area ◽  
Knockout Mice ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Nigrostriatal System ◽  
Ventral Tegmental

Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson’s disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration. Here we have studied the dynamics of changes in TH-positive cell numbers in the SN and VTA during a critical period of their embryonic development in alpha-synuclein knockout mice. This precise study of DA neurons during development of the SN revealed that not only is the number of DA neurons reduced by the end of the period of ontogenic selection, but that the way these neurons are formed is altered in alpha-synuclein knockout mice. At the same time, DA neurons in the VTA are not affected. Alpha-synuclein exerts a modulating effect on the formation of DA neurons in the SN and has no effect on the formation of DA neurons in VTA, the structure that is much less susceptible to degeneration in a brain with PD, suggesting a potential role of alpha-synuclein in the development of the population of DA neurons in substantia nigra.

scholarly journals Genetic inactivation of alpha-synuclein affects embryonic development of dopaminergic neurons of the substantia nigra but not the ventral tegmental area in mouse brain

2018 ◽  
Author(s):  
Tatyana V Tarasova ◽  
Olga A Lytkina ◽  
Valeria V Goloborshcheva ◽  
Larisa N Skuratovskaya ◽  
Alexandr I Antohin ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Embryonic Development ◽  
Ventral Tegmental Area ◽  
Knockout Mice ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Nigrostriatal System ◽  
Ventral Tegmental

Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson's disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration. Here we have studied the dynamics of changes in TH-positive cell numbers in the SN and VTA during a critical period of their embryonic development in alpha-synuclein knockout mice. This precise study of DA neurons during development of the SN revealed that not only is the number of DA neurons reduced by the end of the period of ontogenic selection, but that the way these neurons are formed is altered in alpha-synuclein knockout mice. At the same time, DA neurons in the VTA are not affected. Alpha-synuclein exerts a modulating effect on the formation of DA neurons in the SN and has no effect on the formation of DA neurons in VTA, the structure that is much less susceptible to degeneration in PD brain, suggesting a potential role of alpha-synuclein in the development of the population of DA neurons in substantia nigra.

Modulatory role of the orexin system in stress‐induced analgesia: Involvement of the ventral tegmental area

2021 ◽  
Author(s):  
Kobra Askari ◽  
Shahrbanoo Oryan ◽  
Akram Eidi ◽  
Jalal Zaringhalam ◽  
Abbas Haghparast
Keyword(s):  
Ventral Tegmental Area ◽  
Ventral Tegmental

scholarly journals The laterodorsal tegmentum-ventral tegmental area circuit controls depression-like behaviors by activating ErbB4 in DA neurons

2021 ◽  
Author(s):  
Hongsheng Wang ◽  
Wanpeng Cui ◽  
Wenbing Chen ◽  
Fang Liu ◽  
Zhaoqi Dong ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Coping With Stress ◽  
Chemical Genetic ◽  
Chronic Social Defeat Stress ◽  
Ventral Tegmental ◽  
Laterodorsal Tegmentum ◽  
Specific Deletion

AbstractDopamine (DA) neurons in the ventral tegmental area (VTA) are critical to coping with stress. However, molecular mechanisms regulating their activity and stress-induced depression were not well understood. We found that the receptor tyrosine kinase ErbB4 in VTA was activated in stress-susceptible mice. Deleting ErbB4 in VTA or in DA neurons, or chemical genetic inhibition of ErbB4 kinase activity in VTA suppressed the development of chronic social defeat stress (CSDS)-induced depression-like behaviors. ErbB4 activation required the expression of NRG1 in the laterodorsal tegmentum (LDTg); LDTg-specific deletion of NRG1 inhibited depression-like behaviors. NRG1 and ErbB4 suppressed potassium currents of VTA DA neurons and increased their firing activity. Finally, we showed that acute inhibition of ErbB4 after stress attenuated DA neuron hyperactivity and expression of depression-like behaviors. Together, these observations demonstrate a critical role of NRG1-ErbB4 signaling in regulating depression-like behaviors and identify an unexpected mechanism by which the LDTg-VTA circuit regulates the activity of DA neurons.

scholarly journals Inflammatory Pain Promotes Increased Opioid Self-Administration: Role of Dysregulated Ventral Tegmental Area   Opioid Receptors

2015 ◽  
Vol 35 (35) ◽  
pp. 12217-12231 ◽  
Author(s):  
L. Hipolito ◽  
A. Wilson-Poe ◽  
Y. Campos-Jurado ◽  
E. Zhong ◽  
J. Gonzalez-Romero ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Opioid Receptors ◽  
Inflammatory Pain ◽  
Self Administration ◽  
Ventral Tegmental
Sign in / Sign up

Export Citation Format

Share Document