scholarly journals Molecular and functional differences in voltage-activated sodium currents between GABA projection neurons and dopamine neurons in the substantia nigra

2011 ◽  
Vol 106 (6) ◽  
pp. 3019-3034 ◽  
Author(s):  
Shengyuan Ding ◽  
Wei Wei ◽  
Fu-Ming Zhou
Keyword(s):  
Substantia Nigra ◽  
Low Frequency ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Pcr Analysis ◽  
Projection Neurons ◽  
Na Current ◽  
Gaba Neurons ◽  
Voltage Dependent ◽  
Firing Properties

GABA projection neurons (GABA neurons) in the substantia nigra pars reticulata (SNr) and dopamine projection neurons (DA neurons) in substantia nigra pars compacta (SNc) have strikingly different firing properties. SNc DA neurons fire low-frequency, long-duration spikes, whereas SNr GABA neurons fire high-frequency, short-duration spikes. Since voltage-activated sodium (NaV) channels are critical to spike generation, the different firing properties raise the possibility that, compared with DA neurons, NaV channels in SNr GABA neurons have higher density, faster kinetics, and less cumulative inactivation. Our quantitative RT-PCR analysis on immunohistochemically identified nigral neurons indicated that mRNAs for pore-forming NaV1.1 and NaV1.6 subunits and regulatory NaVβ1 and Navβ4 subunits are more abundant in SNr GABA neurons than SNc DA neurons. These α-subunits and β-subunits are key subunits for forming NaV channels conducting the transient NaV current ( INaT), persistent Na current ( INaP), and resurgent Na current ( INaR). Nucleated patch-clamp recordings showed that INaT had a higher density, a steeper voltage-dependent activation, and a faster deactivation in SNr GABA neurons than in SNc DA neurons. INaT also recovered more quickly from inactivation and had less cumulative inactivation in SNr GABA neurons than in SNc DA neurons. Furthermore, compared with nigral DA neurons, SNr GABA neurons had a larger INaR and INaP. Blockade of INaP induced a larger hyperpolarization in SNr GABA neurons than in SNc DA neurons. Taken together, these results indicate that NaV channels expressed in fast-spiking SNr GABA neurons and slow-spiking SNc DA neurons are tailored to support their different spiking capabilities.

scholarly journals Kv3-Like Potassium Channels Are Required for Sustained High-Frequency Firing in Basal Ganglia Output Neurons

2011 ◽  
Vol 105 (2) ◽  
pp. 554-570 ◽  
Author(s):  
Shengyuan Ding ◽  
Shannon G. Matta ◽  
Fu-Ming Zhou
Keyword(s):  
Basal Ganglia ◽  
High Frequency ◽  
Movement Control ◽  
Dopamine Neurons ◽  
Pcr Analysis ◽  
Delayed Rectifier ◽  
Projection Neurons ◽  
Gaba Neurons ◽  
Fast Spiking ◽  
Output Neurons

The GABA projection neurons in the substantial nigra pars reticulata (SNr) are key output neurons of the basal ganglia motor control circuit. These neurons fire sustained high-frequency, short-duration spikes that provide a tonic inhibition to their targets and are critical to movement control. We hypothesized that a robust voltage-activated K+ conductance that activates quickly and resists inactivation is essential to the remarkable fast-spiking capability in these neurons. Semi-quantitative RT-PCR (qRT-PCR) analysis on laser capture-microdissected nigral neurons indicated that mRNAs for Kv3.1 and Kv3.4, two key subunits for forming high activation threshold, fast-activating, slow-inactivating, 1 mM tetraethylammonium (TEA)-sensitive, fast delayed rectifier ( IDR-fast) type Kv channels, are more abundant in fast-spiking SNr GABA neurons than in slow-spiking nigral dopamine neurons. Nucleated patch clamp recordings showed that SNr GABA neurons have a strong Kv3-like IDR-fast current sensitive to 1 mM TEA that activates quickly at depolarized membrane potentials and is resistant to inactivation. IDR-fast is smaller in nigral dopamine neurons. Pharmacological blockade of IDR-fast by 1 mM TEA impaired the high-frequency firing capability in SNr GABA neurons. Taken together, these results indicate that Kv3-like channels mediating fast-activating, inactivation-resistant IDR-fast current are critical to the sustained high-frequency firing in SNr GABA projection neurons and hence movement control.

scholarly journals An unconventional conductance is required for pacemaking of nigral dopamine neurons

2020 ◽  
Author(s):  
Kevin Jehasse ◽  
Laurent Massotte ◽  
Sebastian Hartmann ◽  
Romain Vitello ◽  
Sofian Ringlet ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Sodium Channels ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Voltage Gated ◽  
Molecular Identity ◽  
Voltage Gated Sodium Channels ◽  
Voltage Dependent ◽  
Ionic Mechanisms ◽  
Voltage Gated Channels

ABSTRACTAlthough several ionic mechanisms are known to control rate and regularity of the pacemaker in dopamine (DA) neurons from the substantia nigra pars compacta (SNc), a conductance essential for pacing has yet to be defined. Here we provide pharmacological evidence that pacemaking of SNc DA neurons is enabled by an unconventional conductance. We found that 1-(2,4-xylyl)guanidine (XG), an established blocker of gating pore currents in mutant voltage gated sodium channels, selectively stops pacemaking of DA SNc neurons and is without effect on the main pore of their voltage-gated channels. We isolated a voltage-dependent, non-inactivating XG-sensitive current of 20-25 pA which operates in the relevant subthreshold range and is carried by both Na+ and Cl- ions. While the molecular identity of this conductance remains to be determined, we show that this XG-sensitive current is crucial to sustain pacemaking in these neurons.

scholarly journals The tectonigral pathway regulates appetitive locomotion in predatory hunting in mice

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.

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

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.

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

2014 ◽  
Vol 3 (3) ◽  
pp. 240-242 ◽  
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

Parkinson’s 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 Parkinson’s 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

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

2021 ◽  
Author(s):  
Marcelo D Mendonça ◽  
Joaquim Alves da Silva ◽  
Ledia F. Hernandez ◽  
Ivan Castela ◽  
José Obeso ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Neuron Activity ◽  
Similar Proportion ◽  
List Type ◽  
Dopamine Depletion ◽  
Movement Initiation ◽  
Transient Activity ◽  
Forelimb Movement

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.

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

1999 ◽  
Vol 82 (4) ◽  
pp. 1974-1981 ◽  
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.

Distinct Mechanisms of Presynaptic Inhibition at GABAergic Synapses of the Rat Substantia Nigra Pars Compacta

2005 ◽  
Vol 94 (3) ◽  
pp. 1992-2003 ◽  
Author(s):  
Michela Giustizieri ◽  
Giorgio Bernardi ◽  
Nicola B. Mercuri ◽  
Nicola Berretta
Keyword(s):  
Substantia Nigra ◽  
Presynaptic Inhibition ◽  
Metabotropic Glutamate Receptors ◽  
Calcium Ionophore ◽  
Gaba Release ◽  
Substantia Nigra Pars Compacta ◽  
Gabaergic Neurotransmission ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Voltage Dependent

We investigated the mechanisms of presynaptic inhibition of GABAergic neurotransmission by group III metabotropic glutamate receptors (mGluRs) and GABAB receptors, in dopamine (DA) neurons of the substantia nigra pars compacta (SNc). Both the group III mGluRs agonist l-(+)-2-amino-4-phosphonobutyric acid (AP4, 100 μM) and the GABAB receptor agonist baclofen (10 μM) reversibly depressed the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) to 48.5 ± 2.7 and 79.3 ± 1.6% (means ± SE) of control, respectively. On the contrary, the frequency of action potential-independent miniature IPSCs (mIPSCs), recorded in tetrodotoxin (TTX, 1 μM) and cadmium (100 μM) were insensitive to AP4 but were reduced by baclofen to 49.7 ± 8.6% of control. When the contribution of voltage-dependent calcium channels (VDCCs) to synaptic transmission was boosted with external barium (1 mM), AP4 became effective in reducing TTX-resistant mIPSCs to 65.4 ± 3.9% of control, thus confirming a mechanism of presynaptic inhibition involving modulation of VDCCs. Differently from AP4, baclofen inhibited to 58.5 ± 6.7% of control the frequency mIPSCs recorded in TTX and the calcium ionophore ionomycin (2 μM), which promotes Ca2+-dependent, but VDCC-independent, transmitter release. Moreover, in the presence of α-latrotoxin (0.3 nM), to promote a Ca2+-independent vesicular release of GABA, baclofen reduced mIPSC frequency to 48.1 ± 3.2% of control, while AP4 was ineffective. These results indicate that group III mGluRs depress GABA release to DA neurons of the SNc through inhibition of presynaptic VDCCs, while presynaptic GABAB receptors directly impair transmitter exocytosis.

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