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 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 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.

Struktur und Efferenzen der Substantia nigra pars compacta beim idiopathischen Parkinson-Syndrom

2020 ◽  
Vol 88 (09) ◽  
pp. 591-599
Author(s):  
Peter Urban ◽  
Bjorn Falkenburger ◽  
Wolfgang H. Jost ◽  
Gerhard Ransmayr ◽  
Peter Riederer ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Substantia Nigra Pars Compacta

ZusammenfassungEs besteht Konsens, dass das neuropathologische Merkmal des idiopathischen Parkinson-Syndroms (IPS) der neuronale Zellverlust der Substantia nigra pars compacta (SNc) in Verbindung mit einer Lewy-Pathologie ist. Die transsynaptische Ausbreitung der Lewy-Pathologie wird als wesentlich in der Parkinson-Pathogenese angesehen. Daher ist die Kenntnis präexistenter neuroanatomischer Verbindungen der SNc wesentlich. Wir beschreiben hier neuere tierexperimentelle Befunde zu den afferenten und efferenten Projektionen der SNc und diskutieren die Evidenz für und gegen die sequentielle transsynaptische Ausbreitung der Lewy-Pathologie in der Pathogenese des IPS.

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.

Sign in / Sign up

Export Citation Format

Share Document