scholarly journals Action potential and calcium dependence of tonic somatodendritic dopamine release in the Substantia Nigra pars compacta

2018 ◽  
Vol 148 (4) ◽  
pp. 462-479 ◽  
Author(s):  
Andrew G. Yee ◽  
Blaze Forbes ◽  
Pang-Ying Cheung ◽  
Alessandro Martini ◽  
Mark H. Burrell ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Action Potential ◽  
Dopamine Release ◽  
Substantia Nigra Pars Compacta ◽  
Calcium Dependence

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.

Characteristics of Electrically Evoked Somatodendritic Dopamine Release in Substantia Nigra and Ventral Tegmental Area In Vitro

1997 ◽  
Vol 77 (2) ◽  
pp. 853-862 ◽  
Author(s):  
M. E. Rice ◽  
S. J. Cragg ◽  
S. A. Greenfield
Keyword(s):  
Electrical Stimulation ◽  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Dopamine Release ◽  
Substantia Nigra Pars Compacta ◽  
Frequency Dependent ◽  
Body Regions ◽  
Ventral Tegmental ◽  
Da Release

Rice, M. E., S. J. Cragg, and S. A. Greenfield. Characteristics of electrically evoked somatodendritic dopamine release in substantia nigra and ventral tegmental area in vitro. J. Neurophysiol. 77: 853–862, 1997. Somatodendritic dopamine (DA) release from neurons of the midbrain represents a nonclassical form of neuronal signaling. We assessed characteristics of DA release during electrical stimulation of the substantia nigra pars compacta (SNc) in guinea pig midbrain slices. With the use of parameters optimized for this region, we compared stimulus-induced increases in extracellular DA concentration ([DA]o) in medial and lateral SNc, ventral tegmental area (VTA), and dorsal striatum in vitro. DA release was monitored directly with carbon-fiber microelectrodes and fast-scan cyclic voltammetry. Detection of DA in SNc was confirmed by electrochemical, pharmacological, and anatomic criteria. Voltammograms of the released substance had the same peak potentials as those of DA obtained during in vitro calibration, but different from those of the indoleamine 5-hydroxytryptamine. Similar voltammograms were also obtained in the DA-rich striatum during local electrical stimulation. Contribution from the DA metabolite 3,4-dihydroxyphenylacetic acid to somatodendritic release was negligible, as indicated by the lack of effect of the monoamine oxidase inhibitor pargyline (20 μM) on the signal. Lastly, DA voltammograms could only be elicited in regions that were subsequently determined to be positive for tyrosine hydroxylase immunoreactivity (TH-ir). The frequency dependence of stimulated DA release in SNc was determined over a range of 1–50 Hz, with a constant duration of 10 s. Release was frequency dependent up to 10 Hz, with no further increase at higher frequencies. Stimulation at 10 Hz was used in all subsequent experiments. With this paradigm, DA release in SNc was tetrodotoxin insensitive, but strongly Ca2+ dependent. Stimulated [DA]o in the midbrain was also site specific. At the midcaudal level examined, DA efflux was significantly greater in VTA (1.04 ± 0.05 μM, mean ± SE) than in medial SNc (0.52 ± 0.05 μM), which in turn was higher than in lateral SNc (0.35 ± 0.03 μM). This pattern followed the apparent density of TH-ir, which was also VTA > medial SNc > lateral SNc. This report has introduced a new paradigm for the study of somatodendritic DA release. Voltammetric recording with electrodes of 2–4 μm tip diameter permitted highly localized, direct detection of endogenous DA. The Ca2+ dependence of stimulated release indicated that the process was physiologically relevant. Moreover, the findings that somatodendritic release was frequency dependent across a range characteristic of DA cell firing rates and that stimulated [DA]o varied markedly among DA cell body regions have important implications for how dendritically released DA may function in the physiology and pathophysiology of substantia nigra and VTA.

scholarly journals Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons

2021 ◽  
Author(s):  
Alexis Haddjeri-Hopkins ◽  
Mónica Tapia ◽  
Jorge Ramirez-Franco ◽  
Fabien Tell ◽  
Béatrice Marqueze-Pouey ◽  
...  
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Substantia Nigra ◽  
Action Potential ◽  
Inhibitory Response ◽  
Substantia Nigra Pars Compacta ◽  
Antigen Retrieval ◽  
Biophysical Property ◽  
Gating Kinetics ◽  
Hyperpolarization Activated Current

ABSTRACTSubstantia nigra pars compacta (SNc) dopaminergic (DA) neurons display a peculiar electrical phenotype characterized in vitro by a spontaneous tonic regular activity (pacemaking activity), a broad action potential and a biphasic post-inhibitory response. Several studies in rodents have underlined the central role played by the transient A-type current (IA) in the control of pacemaking activity and post-inhibitory rebound properties, thereby influencing both DA release and the physiological response of SNc neurons to incoming inhibitory inputs. Kv4.3 potassium channels were considered to be fully responsible for IA in these neurons, their density being tightly related to pacemaking frequency. In spite of this crucial electrophysiological role, we show that Kv4.3-/- transgenic mice exhibit minor alterations in locomotion and motor learning, although no compensation by functionally overlapping ion channels is observed in Kv4.3-/- SNc DA neurons. Using antigen retrieval immunohistochemistry, we further demonstrate that Kv4.2 potassium channels are also expressed in SNc DA neurons, even though their contribution to IA appears significant only in a minority of neurons (~5-10%). Using correlative analysis on recorded electrophysiological parameters and multi-compartment modeling, we then demonstrate that, rather than its conductance level, IA gating kinetics (inactivation time constant) appear as the main biophysical property defining post-inhibitory rebound delay and pacemaking frequency. Moreover, we show that the hyperpolarization-activated current (IH) has an opposing and complementary influence on the same firing features, and that the biophysical properties of IA and IH are likely coregulated in mouse SNc DA neurons.SIGNIFICANCE STATEMENTSubstantia nigra pars compacta (SNc) dopaminergic (DA) neurons are characterized by pacemaking activity, a broad action potential and biphasic post-inhibitory response. The A-type transient potassium current (IA) plays a central role in both pacemaking activity and post-inhibitory response. While it was thought so far that Kv4.3 ion channels were fully responsible for IA, using a Kv4.3-/- transgenic mouse and antigen retrieval immunohistochemistry we demonstrate that Kv4.2 channels are also expressed in SNc DA neurons, although their contribution is significant in a minority of neurons only. Using electrophysiological recordings and computational modeling, we then demonstrate that IA gating kinetics and its functional complementarity with the hyperpolarization-activated current are major determinants of both pacemaking activity and post-inhibitory response in SNc DA neurons.

scholarly journals A dual role for α-synuclein in facilitation and depression of dopamine release from substantia nigra neurons in vivo

2020 ◽  
Vol 117 (51) ◽  
pp. 32701-32710
Author(s):  
Mahalakshmi Somayaji ◽  
Stefano Cataldi ◽  
Se Joon Choi ◽  
Robert H. Edwards ◽  
Eugene V. Mosharov ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Action Potential ◽  
Synaptic Vesicle ◽  
Neuronal Activity ◽  
Dopamine Release ◽  
Short Intervals ◽  
Presynaptic Plasticity ◽  
Presynaptic Calcium ◽  
Synaptic Vesicle Fusion

α-Synuclein is expressed at high levels at presynaptic terminals, but defining its role in the regulation of neurotransmission under physiologically relevant conditions has proven elusive. We report that, in vivo, α-synuclein is responsible for the facilitation of dopamine release triggered by action potential bursts separated by short intervals (seconds) and a depression of release with longer intervals between bursts (minutes). These forms of presynaptic plasticity appear to be independent of the presence of β- and γ-synucleins or effects on presynaptic calcium and are consistent with a role for synucleins in the enhancement of synaptic vesicle fusion and turnover. These results indicate that the presynaptic effects of α-synuclein depend on specific patterns of neuronal activity.

scholarly journals MORPHOLOGICAL DETERMINANTS OF CELL-TO-CELL VARIATIONS IN ACTION POTENTIAL DYNAMICS IN SUBSTANTIA NIGRA DOPAMINERGIC NEURONS

2021 ◽  
Author(s):  
Estelle Moubarak ◽  
Yanis Inglebert ◽  
Fabien Tell ◽  
Jean-Marc Goaillard
Keyword(s):  
Substantia Nigra ◽  
Action Potential ◽  
Sodium Channels ◽  
Neurotransmitter Release ◽  
Dopaminergic Neurons ◽  
Dendritic Morphology ◽  
Substantia Nigra Pars Compacta ◽  
Electrophysiological Recordings ◽  
Neuronal Types ◽  
Neuronal Type

ABSTRACTAction potential (AP) shape is a critical electrophysiological parameter, in particular because it strongly modulates neurotransmitter release. AP shape is also used to distinguish neuronal populations, as it greatly varies between neuronal types. For instance, AP duration ranges from hundreds of microseconds in cerebellar granule cells to 2-3 milliseconds in substantia nigra pars compacta (SNc) dopaminergic (DA) neurons. While most of this variation seems to arise from differences in the subtypes of voltage- and calcium-gated ion channels expressed, a few studies suggested that dendritic morphology may also affect AP shape. However, AP duration also displays significant variability in a same neuronal type, while the determinants of these variations are poorly known. Using electrophysiological recordings, morphological reconstructions and realistic Hodgkin-Huxley modeling, we investigated the relationships between dendritic morphology and AP shape in SNc DA neurons. In this neuronal type where the axon arises from an axon-bearing dendrite (ABD), the duration of the somatic AP could be predicted from a linear combination of the complexities of the ABD and the non-ABDs. Dendrotomy simulation and experiments showed that these correlations arise from the causal influence of dendritic topology on AP duration, due in particular to a high density of sodium channels in the somato-dendritic compartment. In addition, dendritic morphology also modulated AP back-propagation efficiency in response to barrages of EPSCs in the ABD. In line with previous findings, these results demonstrate that dendritic morphology plays a major role in defining the electrophysiological properties of SNc DA neurons and their cell-to-cell variations.SIGNIFICANCE STATEMENTAction potential (AP) shape is a critical electrophysiological parameter, in particular because it strongly modulates neurotransmitter release. AP shape (e.g. duration) greatly varies between neuronal types but also within a same neuronal type. While differences in ion channel expression seem to explain most of AP shape variation across cell types, the determinants of cell-to-cell variations in a same neuronal type are mostly unknown. We used electrophysiological recordings, neuronal reconstruction and modeling to show that, due to the presence of sodium channels in the somato-dendritic compartment, a large part of cell-to-cell variations in somatic AP duration in substantia nigra pars compacta dopaminergic neurons is explained by variations in dendritic topology.

scholarly journals The SC-SNc pathway boosts appetitive locomotion in predatory hunting

2020 ◽  
Author(s):  
Meizhu Huang ◽  
Dapeng Li ◽  
Qing Pei ◽  
Zhiyong Xie ◽  
Huating Gu ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Superior Colliculus ◽  
Dopamine Release ◽  
Dorsal Striatum ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Locomotion Speed ◽  
Brain Circuit ◽  
Goal Directed Behavior ◽  
The Brain

ABSTRACTAppetitive locomotion is essential for organisms to approach rewards, such as food and prey. How the brain controls appetitive locomotion is poorly understood. In a naturalistic goal-directed behavior—predatory hunting, we demonstrate an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to boost appetitive locomotion. The SC-SNc pathway transmitted locomotion-speed signals to dopamine neurons and triggered dopamine release in the dorsal striatum. Activation of this pathway increased the speed and frequency of approach during predatory hunting, an effect that depended on the activities of SNc dopamine neurons. Conversely, synaptic inactivation of this pathway impaired appetitive locomotion but not defensive or exploratory locomotion. Together, these data revealed the SC as an important source to provide locomotion-related signals to SNc dopamine neurons to boost appetitive locomotion.

Modulation of Somatodendritic Dopamine Release by Endogenous H2O2: Susceptibility in Substantia Nigra But Resistance in VTA

2002 ◽  
Vol 87 (2) ◽  
pp. 1155-1158 ◽  
Author(s):  
Billy T. Chen ◽  
Marat V. Avshalumov ◽  
Margaret E. Rice
Keyword(s):  
Nucleus Accumbens ◽  
Substantia Nigra ◽  
Dopamine Release ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
Substantia Nigra Pars Compacta ◽  
Fast Scan Cyclic Voltammetry ◽  
Carbon Fiber Microelectrodes ◽  
Da Release ◽  
Striking Contrast

We showed previously that dopamine (DA) release in dorsal striatum is inhibited by endogenously generated hydrogen peroxide (H2O2). Here, we examined whether endogenous H2O2 can also modulate somatodendritic DA release in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), with companion measurements in DA terminal regions. Evoked DA release was monitored in brain slices using carbon-fiber microelectrodes with fast-scan cyclic voltammetry. Exogenous H2O2decreased DA release by 50–60% in SNc and VTA but only by 35% in nucleus accumbens. Whether endogenous H2O2 also modulated somatodendritic release was examined using the glutathione peroxidase inhibitor, mercaptosuccinate (MCS), which should increase stimulation-evoked H2O2levels. In the presence of MCS, DA release was suppressed by 30–40% in SNc as well as in dorsal striatum and nucleus accumbens. In striking contrast, DA release in the VTA was unaffected by MCS. These data are consistent with stronger H2O2 regulation or lower H2O2 generation in VTA than in the other regions. Importantly, oxidative stress has been linked causally to Parkinson's disease, in which DA cells in SNc degenerate, but VTA cells are spared. The present data suggest that differences in oxidant regulation or generation between SNc and VTA could contribute to this.

scholarly journals α-Synuclein facilitates dopamine release during burst firing of substantia nigra neurons in vivo

2020 ◽  
Author(s):  
Mahalakshmi Somayaji ◽  
Stefano Cataldi ◽  
Robert H. Edwards ◽  
Eugene V. Mosharov ◽  
David Sulzer
Keyword(s):  
Substantia Nigra ◽  
Action Potential ◽  
Synaptic Vesicle ◽  
Neuronal Activity ◽  
Dopamine Release ◽  
Vesicle Fusion ◽  
Burst Firing ◽  
Presynaptic Calcium ◽  
Synaptic Vesicle Fusion

Abstractα-Synuclein is expressed at high levels at presynaptic terminals, but defining its role on neurotransmission under physiologically-relevant conditions has proven elusive. We report that α-synuclein is responsible for a rapid facilitation of dopamine release during action potential bursts in vivo. This occurs in tandem with a far slower stimulus-dependent depression, appears to be independent of the presence of β- and γ-synucleins or effects on presynaptic calcium and is consistent with a role for synucleins in the enhancement of synaptic vesicle fusion and turnover. The results indicate that the presynaptic effects of α-synuclein are dependent on specific patterns of neuronal activity.

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