Transient dopamine neuron activity precedes and encodes the vigor of contralateral movements

SummaryDopamine neurons (DANs) in the substantia nigra pars compacta (SNc) have been related to movement vigor, and loss of these neurons leads to bradykinesia in Parkinson’s disease. However, it remains unclear whether DANs encode a general motivation signal or modulate movement kinematics. We imaged activity of SNc DANs in mice trained in a novel operant task which relies on individual forelimb movement sequences. We uncovered that a similar proportion of SNc DANs increased their activity before ipsi- vs. contralateral forelimb movements. However, the magnitude of this activity was higher for contralateral actions, and was related to contralateral but not ipsilateral action vigor. In contrast, the activity of reward-related DANs, largely distinct from those modulated by movement, was not lateralized. Finally, unilateral dopamine depletion impaired contralateral, but not ipsilateral, movement vigor. These results indicate that movement-initiation DANs encode more than a general motivation signal, and invigorate kinematic aspects of contralateral movements.HighlightsDeveloped a freely-moving task where mice learn rapid individual forelimb sequences.Movement-related DANs encode contralateral but not ipsilateral action vigor.The activity of reward-related DANs is not lateralized.Unilateral dopamine depletion impaired contralateral, but not ipsilateral, movement vigor.eTOC summary: Mendonça et al. show that transient activity in movement-related dopamine neurons in substantia nigra pars compacta encodes contralateral, but not ipsilateral action vigor. Consistently, unilateral dopamine depletion impaired contralateral, but not ipsilateral, movement vigor.

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The tectonigral pathway regulates appetitive locomotion in predatory hunting in mice

Nature Communications ◽

10.1038/s41467-021-24696-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Meizhu Huang ◽

Dapeng Li ◽

Xinyu Cheng ◽

Qing Pei ◽

Zhiyong Xie ◽

...

Keyword(s):

Substantia Nigra ◽

Superior Colliculus ◽

Dopamine Release ◽

Dorsal Striatum ◽

Dopamine Neurons ◽

Substantia Nigra Pars Compacta ◽

Neuronal Circuitry ◽

Locomotion Speed ◽

Brain Circuit ◽

Goal Directed Behavior

AbstractAppetitive locomotion is essential for animals to approach rewards, such as food and prey. The neuronal circuitry controlling appetitive locomotion is unclear. In a goal-directed behavior—predatory hunting, we show an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to enhance appetitive locomotion in mice. This tectonigral pathway transmits locomotion-speed signals to dopamine neurons and triggers dopamine release in the dorsal striatum. Synaptic inactivation of this pathway impairs appetitive locomotion but not defensive locomotion. Conversely, activation of this pathway increases the speed and frequency of approach during predatory hunting, an effect that depends on the activities of SNc dopamine neurons. Together, these data reveal that the SC regulates locomotion-speed signals to SNc dopamine neurons to enhance appetitive locomotion in mice.

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Substantia nigra neuromelanin magnetic resonance imaging in patients with different subtypes of Parkinson disease

Journal of Neural Transmission ◽

10.1007/s00702-020-02295-8 ◽

2021 ◽

Author(s):

Lu Wang ◽

Yayun Yan ◽

Liyao Zhang ◽

Yan Liu ◽

Ruirui Luo ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Substantia Nigra ◽

Parkinson Disease ◽

Clinical Symptoms ◽

Dopamine Neurons ◽

Substantia Nigra Pars Compacta ◽

Resonance Imaging ◽

Mean Values

AbstractNeuromelanin (NM) is a dark pigment that mainly exists in neurons of the substantia nigra pars compacta (SNc). In Parkinson disease (PD) patients, NM concentration decreases gradually with degeneration and necrosis of dopamine neurons, suggesting potential use as a PD biomarker. We aimed to evaluate associations between NM concentration in in vivo SN and PD progression and different motor subtypes using NM magnetic resonance imaging (NM-MRI). Fifty-four patients with idiopathic PD were enrolled. Patients were divided into groups by subtypes with different clinical symptoms: tremor dominant (TD) group and postural instability and gait difficulty (PIGD) group. Fifteen healthy age-matched volunteers were enrolled as controls. All subjects underwent clinical assessment and NM-MRI examination. PD patients showed significantly decreased contrast-to-noise ratio (CNR) values in medial and lateral SN (P < 0.05) compared to controls. CNR values in lateral SN region decreased linearly with PD progression (P = 0.001). PIGD patients showed significant decreases in CNR mean values in lateral SN compared to TD patients (P = 0.004). Diagnostic accuracy of using lateral substantia nigra (SN) in TD and PIGD groups was 79% (sensitivity 76.5%, specificity 78.6%). NM concentration in PD patients decreases gradually during disease progression and differs significantly between PD subtypes. NM may be a reliable biomarker for PD severity and subtype identification.

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Effect of various extracts of Tabernaemontana divaricata on haloperidol induced catalepsy in rats

International Current Pharmaceutical Journal ◽

10.3329/icpj.v3i3.17891 ◽

2014 ◽

Vol 3 (3) ◽

pp. 240-242 ◽

Cited By ~ 1

Author(s):

Chanchal N. Raj ◽

A. Balasubramaniam ◽

Sayyed Nadeem

Keyword(s):

Animal Model ◽

Substantia Nigra ◽

Neurodegenerative Diseases ◽

Pharmaceutical Journal ◽

Dopamine Neurons ◽

Substantia Nigra Pars Compacta ◽

Selective Loss ◽

Tabernaemontana Divaricata ◽

Medicinal Use ◽

Different Doses

Parkinsons disease (PD) is one of the neurodegenerative diseases with selective loss of dopamine neurons of the substantia nigra pars compacta. In the present study, anti-cataleptic activity of Tabernaemontana divaricata leaves extracts viz. aqueous and ethanolic at different doses (50, 100 and 150 mg/kg i.p.) were studied using haloperidol (1 mg/kg, i.p.) induced catalepsy in rats which is a useful animal model for screening drugs for Parkinsons disease. Both the extracts were found to reduce catalepsy significantly (P<0.001) as compared to the haloperidol treated rats showing greater effect at 150 mg/kg i.p. dose. Thus the present study reveals the anti-cataleptic activity of Tabernaemontana divaricata evaluating the traditional folklore medicinal use of the plant.DOI: http://dx.doi.org/10.3329/icpj.v3i3.17891 International Current Pharmaceutical Journal, February 2014, 3(3): 240-242

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Voltage-operated Ca2+ channels regulate dopamine release from somata of dopamine neurons in the substantia nigra pars compacta

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2008.06.099 ◽

2008 ◽

Vol 373 (4) ◽

pp. 665-669 ◽

Cited By ~ 13

Author(s):

Yonjung Kim ◽

Myoung Kyu Park ◽

Sungkwon Chung

Keyword(s):

Substantia Nigra ◽

Dopamine Release ◽

Dopamine Neurons ◽

Substantia Nigra Pars Compacta ◽

Ca2 Channels

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Group I Metabotropic Glutamate Receptors Mediate an Inward Current in Rat Substantia Nigra Dopamine Neurons That Is Independent From Calcium Mobilization

Journal of Neurophysiology ◽

10.1152/jn.1999.82.4.1974 ◽

1999 ◽

Vol 82 (4) ◽

pp. 1974-1981 ◽

Cited By ~ 47

Author(s):

Ezia Guatteo ◽

Nicola B. Mercuri ◽

Giorgio Bernardi ◽

Thomas Knöpfel

Keyword(s):

Substantia Nigra ◽

Glutamate Receptors ◽

Metabotropic Glutamate Receptors ◽

Excitatory Amino Acid ◽

Dopamine Neurons ◽

Substantia Nigra Pars Compacta ◽

Inward Current ◽

Metabotropic Glutamate ◽

Group I ◽

Rat Substantia Nigra

Metabotropic glutamate receptors modulate neuronal excitability via a multitude of mechanisms, and they have been implicated in the pathogenesis of neurodegenerative processes. Here we investigated the responses mediated by group I metabotropic glutamate receptors (mGluRs) in dopamine neurons of the rat substantia nigra pars compacta, using whole cell patch-clamp recordings in combination with microfluorometric measurements of [Ca2+]i and [Na+]i. The selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (3,5-DHPG) was bath-applied (20 μM, 30 s to 2 min) or applied locally by means of short-lasting (2–4 s) pressure pulses, delivered through an agonist-containing pipette positioned close to the cell body of the neuron. 3,5-DHPG evoked an inward current characterized by a transient and a sustained component, the latter of which was uncovered only with long-lasting agonist applications. The fast component coincided with a transient elevation of [Ca2+]i, whereas the total current was associated with a rise in [Na+]i. These responses were not affected either by the superfusion of ionotropic excitatory amino acid antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and d-2-amino-5-phosphono-pentanoic acid (d-APV), nor by the sodium channel blocker tetrodotoxin (TTX). (S)-α-methyl-4-carboxyphenylglycine (S-MCPG) and the more selective mGluR1 antagonist 7(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate (CPCCOEt) depressed both 3,5-DHPG–induced inward current components and, although less effectively, the associated [Ca2+]i elevations. On repeated agonist applications the inward current and the calcium transients both desensitized. The time constant of recovery from desensitization differed significantly between these two responses, being 67.4 ± 4.4 s for the inward current and 28.6 ± 2.7 s for the calcium response. Bathing the tissue in a calcium-free/EGTA medium or adding thapsigargin (1 μM) to the extracellular medium prevented the generation of the [Ca2+]i transient, but did not prevent the activation of the inward current. These electrophysiological and fluorometric results show that the 3,5-DHPG–induced inward current and the [Ca2+]i elevations are mediated by independent pathways downstream the activation of mGluR1.

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Glutamatergic and cholinergic inputs from the pedunculopontine tegmental nucleus to dopamine neurons in the substantia nigra pars compacta

Neuroscience Research ◽

10.1016/0168-0102(94)00869-h ◽

1995 ◽

Vol 21 (4) ◽

pp. 331-342 ◽

Cited By ~ 161

Author(s):

T. Futami ◽

K. Takakusaki ◽

S.T. Kitai

Keyword(s):

Substantia Nigra ◽

Dopamine Neurons ◽

Pedunculopontine Tegmental Nucleus ◽

Substantia Nigra Pars Compacta ◽

Tegmental Nucleus

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Differential Modulation by Nicotine of Substantia Nigra Versus Ventral Tegmental Area Dopamine Neurons

Journal of Neurophysiology ◽

10.1152/jn.00760.2007 ◽

2007 ◽

Vol 98 (6) ◽

pp. 3388-3396 ◽

Cited By ~ 37

Author(s):

J. Russel Keath ◽

Michael P. Iacoviello ◽

Lindy E. Barrett ◽

Huibert D. Mansvelder ◽

Daniel S. McGehee

Keyword(s):

Substantia Nigra ◽

Ventral Tegmental Area ◽

Dorsal Striatum ◽

Dopamine Neurons ◽

Substantia Nigra Pars Compacta ◽

Synaptic Modulation ◽

Afferent Projections ◽

Ventral Tegmental ◽

Midbrain Dopamine ◽

Da Release

Midbrain dopamine (DA) neurons are found in two nuclei, the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). The SNc dopaminergic projections to the dorsal striatum are involved in voluntary movement and habit learning, whereas the VTA projections to the ventral striatum contribute to reward and motivation. Nicotine induces profound DA release from VTA dopamine neurons but substantially less from the SNc. Nicotinic acetylcholine receptor (nAChR) expression differs between these nuclei, but it is unknown whether there are differences in nAChR expression on the afferent projections to these nuclei. Here we have compared the nicotinic modulation of excitatory and inhibitory synaptic inputs to VTA and SNc dopamine neurons. Although nicotine enhances both the excitatory and inhibitory drive to SNc DA cells with response magnitudes similar to those seen in the VTA, the prevalence of these responses in SNc is much lower. We also found that a mixture of nAChR subtypes underlies the synaptic modulation in SNc, further distinguishing this nucleus from the VTA, where α7 nAChRs enhance glutamate inputs and non-α7 receptors enhance GABA inputs. Finally, we compared the nicotine sensitivity of DA neurons in these two nuclei and found larger response magnitudes in VTA relative to SNc. Thus the observed differences in nicotine-induced DA release from VTA and SNc are likely due to differences in nAChR expression on the afferent inputs as well as on the DA neurons themselves. This may explain why nicotine has a greater effect on behaviors associated with the VTA than the SNc.

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