scholarly journals The Dopaminergic Control of Movement-Evolutionary Considerations

2021 ◽  
Vol 22 (20) ◽  
pp. 11284
Author(s):  
Juan Pérez-Fernández ◽  
Marta Barandela ◽  
Cecilia Jiménez-López
Keyword(s):  
Basal Ganglia ◽  
Dopaminergic Neurons ◽  
Dopaminergic System ◽  
Great Part ◽  
Substantia Nigra Pars Compacta ◽  
Motor Deficits ◽  
Motor Responses ◽  
Early Vertebrates ◽  
Characteristic Motor

Dopamine is likely the most studied modulatory neurotransmitter, in great part due to characteristic motor deficits in Parkinson’s disease that arise after the degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNc). The SNc, together with the ventral tegmental area (VTA), play a key role modulating motor responses through the basal ganglia. In contrast to the large amount of existing literature addressing the mammalian dopaminergic system, comparatively little is known in other vertebrate groups. However, in the last several years, numerous studies have been carried out in basal vertebrates, allowing a better understanding of the evolution of the dopaminergic system, especially the SNc/VTA. We provide an overview of existing research in basal vertebrates, mainly focusing on lampreys, belonging to the oldest group of extant vertebrates. The lamprey dopaminergic system and its role in modulating motor responses have been characterized in significant detail, both anatomically and functionally, providing the basis for understanding the evolution of the SNc/VTA in vertebrates. When considered alongside results from other early vertebrates, data in lampreys show that the key role of the SNc/VTA dopaminergic neurons modulating motor responses through the basal ganglia was already well developed early in vertebrate evolution.

scholarly journals Functional neuroimaging of human vocalizations and affective speech

2014 ◽  
Vol 37 (6) ◽  
pp. 554-555 ◽  
Author(s):  
Sascha Frühholz ◽  
David Sander ◽  
Didier Grandjean
Keyword(s):  
Basal Ganglia ◽  
Functional Neuroimaging ◽  
Feedback Processing ◽  
Motor Responses ◽  
Human Specific

AbstractNeuroimaging studies have verified the important integrative role of the basal ganglia during affective vocalizations. They, however, also point to additional regions supporting vocal monitoring, auditory–motor feedback processing, and online adjustments of vocal motor responses. For the case of affective vocalizations, we suggest partly extending the model to fully consider the link between primate-general and human-specific neural components.

scholarly journals Pedunculopontine glutamatergic neurons control spike patterning in substantia nigra dopaminergic neurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Daniel J Galtieri ◽  
Chad M Estep ◽  
David L Wokosin ◽  
Stephen Traynelis ◽  
D James Surmeier
Keyword(s):  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Glutamatergic Synapses ◽  
Glutamatergic Neurons ◽  
Oscillatory Mechanisms ◽  
Goal Directed Behavior ◽  
Stimulation Of

Burst spiking in substantia nigra pars compacta (SNc) dopaminergic neurons is a key signaling event in the circuitry controlling goal-directed behavior. It is widely believed that this spiking mode depends upon an interaction between synaptic activation of N-methyl-D-aspartate receptors (NMDARs) and intrinsic oscillatory mechanisms. However, the role of specific neural networks in burst generation has not been defined. To begin filling this gap, SNc glutamatergic synapses arising from pedunculopotine nucleus (PPN) neurons were characterized using optical and electrophysiological approaches. These synapses were localized exclusively on the soma and proximal dendrites, placing them in a good location to influence spike generation. Indeed, optogenetic stimulation of PPN axons reliably evoked spiking in SNc dopaminergic neurons. Moreover, burst stimulation of PPN axons was faithfully followed, even in the presence of NMDAR antagonists. Thus, PPN-evoked burst spiking of SNc dopaminergic neurons in vivo may not only be extrinsically triggered, but extrinsically patterned as well.

scholarly journals Modeling Basal Ganglia for Understanding Parkinsonian Reaching Movements

2011 ◽  
Vol 23 (2) ◽  
pp. 477-516 ◽  
Author(s):  
K. N. Magdoom ◽  
D. Subramanian ◽  
V. S. Chakravarthy ◽  
B. Ravindran ◽  
Shun-ichi Amari ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Motor Cortex ◽  
Reaching Movements ◽  
Substantia Nigra Pars Compacta ◽  
Temporal Difference ◽  
Indirect Pathway ◽  
Dynamical Disease ◽  
Exploratory Movements ◽  
Dopamine Signal

We present a computational model that highlights the role of basal ganglia (BG) in generating simple reaching movements. The model is cast within the reinforcement learning (RL) framework with correspondence between RL components and neuroanatomy as follows: dopamine signal of substantia nigra pars compacta as the temporal difference error, striatum as the substrate for the critic, and the motor cortex as the actor. A key feature of this neurobiological interpretation is our hypothesis that the indirect pathway is the explorer. Chaotic activity, originating from the indirect pathway part of the model, drives the wandering, exploratory movements of the arm. Thus, the direct pathway subserves exploitation, while the indirect pathway subserves exploration. The motor cortex becomes more and more independent of the corrective influence of BG as training progresses. Reaching trajectories show diminishing variability with training. Reaching movements associated with Parkinson's disease (PD) are simulated by reducing dopamine and degrading the complexity of indirect pathway dynamics by switching it from chaotic to periodic behavior. Under the simulated PD conditions, the arm exhibits PD motor symptoms like tremor, bradykinesia and undershooting. The model echoes the notion that PD is a dynamical disease.

scholarly journals The Nrf2-NLRP3-Caspase1 axis mediates the neuroprotective effects of Celastrol in Parkinson's disease

2020 ◽  
Author(s):  
Chenyu Zhang ◽  
Miao Zhao ◽  
Bingwei Wang ◽  
Zhijie Su ◽  
Bingbing Guo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Motor Deficits ◽  
Inflammasome Activation ◽  
Sequencing Analysis ◽  
Pentacyclic Triterpene ◽  
Neuroprotective Effects ◽  
Neuroprotective Actions

Abstract Background: Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), accompanied by chronic neuroinflammation, oxidative stress, and widespread accumulation of α-synuclein. Celastrol (Cel), a potent anti-inflammatory and anti-oxidative pentacyclic triterpene, has emerged as a neuroprotective agent. However, the mechanisms by which celastrol is neuroprotective in PD has not yet been elucidated. Methods: The MPTP and AAV-mediated human wild-type α-syn overexpression within SNc induced PD mouse models were employed in this study. By using multiple genetically modified mice (Nrf2-KO, NLRP3-KO and Caspase1-KO), we identified that celastrol effectively inhibited the NLRP3 inflammasome activation, mitigated motor deficits and nigrostriatal dopaminergic degeneration through Nrf2-NLRP3-Caspase1 pathway. Results: Here we show that celastrol protected against the loss of dopaminergic neurons, mitigated the neuroinflammation and motor deficits in both MPTP-induced PD mouse model and AAV-mediated human α-syn overexpression PD model. Whole-genome deep sequencing analysis reveals that Nrf2, NLRP3 and Caspase1 in SNc may be associated with the neuroprotective actions of celastrol in PD. Conclusions: These findings suggest that Nrf2-NLRP3-Caspase1 axis may be a key target of celastrol in PD treatment, and highlight the favorable properties linked to neuroprotection of celastrol, making celastrol as a promising disease-modifying agent for PD.

scholarly journals Neuroprotective and Neurorestorative Effects of Holothuria scabra Extract in the MPTP/MPP+-Induced Mouse and Cellular Models of Parkinson’s Disease

2020 ◽  
Vol 14 ◽  
Author(s):  
Kunwadee Noonong ◽  
Prasert Sobhon ◽  
Morakot Sroyraya ◽  
Kulathida Chaithirayanon
Keyword(s):  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Motor Deficits ◽  
Holothuria Scabra ◽  
Cellular Models ◽  
Anti Oxidant ◽  
Pre Treatment ◽  
Induced Apoptosis

Extracts from Holothuria scabra (HS) have been shown to possess anti-inflammation, anti-oxidant and anti-cancer activities. More recently, it was shown to have neuroprotective potential in Caenorhabditis elegans PD model. Here, we assessed whether HS has neuroprotective and neurorestorative effects on dopaminergic neurons in both mouse and cellular models of PD. We found that both pre-treatment and post-treatment with HS improved motor deficits in PD mouse model induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as determined by grid walk test. This was likely mediated by HS protective and restorative effects on maintaining the numbers of dopaminergic neurons and fibers in both substantia nigra pars compacta (SNpc) and striatum. In a cellular model of PD, HS significantly attenuated 1-methyl-4-phenylpyridinium (MPP+)-induced apoptosis of DAergic-like neurons differentiated from SH-SY5Y cells by enhancing the expression of Bcl-2, suppressing the expression of cleaved Caspase 3 and preventing depolarization of mitochondrial membrane. In addition, HS could stimulate the expression of tyrosine hydroxylase (TH) and suppressed the formation of α-synuclein protein. Taken together, our in vivo and in vitro findings suggested that HS is an attractive candidate for the neuroprotection rather than neurorestoration in PD.

THE ROLE OF THE BASAL GANGLIA IN EXPLORATION IN A NEURAL MODEL BASED ON REINFORCEMENT LEARNING

2006 ◽  
Vol 16 (02) ◽  
pp. 111-124 ◽  
Author(s):  
D. SRIDHARAN ◽  
P. S. PRASHANTH ◽  
V. S. CHAKRAVARTHY
Keyword(s):  
Reinforcement Learning ◽  
Basal Ganglia ◽  
State Space ◽  
Chaotic Systems ◽  
Neural Model ◽  
Learning System ◽  
Substantia Nigra Pars Compacta ◽  
Water Pool ◽  
Oscillatory Dynamics

We present a computational model of basal ganglia as a key player in exploratory behavior. The model describes exploration of a virtual rat in a simulated water pool experiment. The virtual rat is trained using a reward-based or reinforcement learning paradigm which requires units with stochastic behavior for exploration of the system's state space. We model the Subthalamic Nucleus-Globus Pallidus externa (STN-GPe) segment of the basal ganglia as a pair of neuronal layers with oscillatory dynamics, exhibiting a variety of dynamic regimes such as chaos, traveling waves and clustering. Invoking the property of chaotic systems to explore state-space, we suggest that the complex exploratory dynamics of STN-GPe system in conjunction with dopamine-based reward signaling from the Substantia Nigra pars compacta (SNc) present the two key ingredients of a reinforcement learning system.

scholarly journals Role of neuron specific enolase as a biomarker in Parkinson’s disease

2021 ◽  
Vol 5 (2) ◽  
pp. 061-068
Author(s):  
Dutta Rajib
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Neuron Specific Enolase ◽  
Alpha Synuclein ◽  
Substantia Nigra Pars Compacta ◽  
Diagnostic Tools ◽  
Clinical Image ◽  
Motor Symptoms

Parkinson’s disease (PD) is thought to be the most common neurodegenerative disease with movement disorder. The key motor symptoms are rigidity, tremor, akinesis/hypokinesia/bradykinesia, and postural instability. However, in our day-to-day clinical practice we tend to see several other symptoms which may be motor or non-motor. Non-motor symptoms (NMS) are quite common and debilitating. The pathological hallmarks of PD are loss of dopaminergic neurons in the substantia nigra pars compacta (SNPc) and accumulation of unfolded or misfolded alpha-synuclein. Diagnosis of PD is difficult in the pre-motor stage. Late diagnosis renders a substantial loss of dopaminergic neurons in SNPc and spread of disease in other parts of the brain. This may manifest as either full blown symptoms requiring multiple medications or may even lead to life threatening condition due to lack of early diagnostic tools and techniques. Biomarkers are required to diagnose PD at a very early stage when prevention is possible. Hence, we see a lot of interest among researchers involved in finding a biomarker specific to the disease. Biomarkers may be clinical, image based, genetic, and biochemical. Cerebrospinal fluid (CSF) and serum markers which may correlate with disease pathophysiology are of great significance. One such molecule which recently gained a lot of attention is neuron-specific enolase (NSE). The main aim of this paper is to highlight the role of NSE in predicting neurodegeneration and neuroinflammation ultimately reflecting damage of brain cells in PD.

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 The essential role of transcription factor Pitx3 in preventing mesodiencephalic dopaminergic neurodegeneration and maintaining neuronal subtype identities during aging

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Ying Wang ◽  
Xi Chen ◽  
Yuanyuan Wang ◽  
Song Li ◽  
Huaibin Cai ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Substantia Nigra Pars Compacta ◽  
Motor Deficits ◽  
Rapid Reduction ◽  
Dopaminergic Neurodegeneration ◽  
Differential Vulnerability ◽  
Progressive Neurodegeneration ◽  
Mature Neurons ◽  
Neuronal Subtype

AbstractPituitary homeobox 3 (Pitx3) is required for the terminal differentiation of nigrostriatal dopaminergic neurons during neuronal development. However, whether Pitx3 contributes to the normal physiological function and cell-type identity of adult neurons remains unknown. To explore the role of Pitx3 in maintaining mature neurons, we selectively deleted Pitx3 in the mesodiencephalic dopaminergic (mdDA) neurons of Pitx3fl/fl/DATCreERT2 bigenic mice using a tamoxifen inducible CreERT2/loxp gene-targeting system. Pitx3fl/fl/DATCreERT2 mice developed age-dependent progressive motor deficits, concomitant with a rapid reduction of striatal dopamine (DA) content and a profound loss of mdDA neurons in the substantia nigra pars compacta (SNc) but not in the adjacent ventral tegmental area (VTA), recapitulating the canonical neuropathological features of Parkinson’s disease (PD). Mechanistic studies showed that Pitx3-deficiency significantly increased the number of cleaved caspase-3+ cells in SNc, which likely underwent neurodegeneration. Meanwhile, the vulnerability of SNc mdDA neurons was increased in Pitx3fl/fl/DATCreERT2 mice, as indicated by an early decline in glial cell line-derived neurotrophic factor (GDNF) and aldehyde dehydrogenase 1a1 (Aldh1a1) levels. Noticeably, somatic accumulation of α-synuclein (α-syn) was also significantly increased in the Pitx3-deficient neurons. Together, our data demonstrate that the loss of Pitx3 in fully differentiated mdDA neurons results in progressive neurodegeneration, indicating the importance of the Pitx3 gene in adult neuronal survival. Our findings also suggest that distinct Pitx3-dependent pathways exist in SNc and VTA mdDA neurons, correlating with the differential vulnerability of SNc and VTA mdDA neurons in the absence of Pitx3.

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