scholarly journals Non-linear developmental trajectory of electrical phenotype in rat substantia nigra pars compacta dopaminergic neurons

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Martial A Dufour ◽  
Adele Woodhouse ◽  
Julien Amendola ◽  
Jean-Marc Goaillard
Keyword(s):  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Critical Role ◽  
Principal Component ◽  
Developmental Trajectory ◽  
Substantia Nigra Pars Compacta ◽  
Developmental Transitions ◽  
Electrophysiological Properties ◽  
Non Linear ◽  
Unbiased Manner

Neurons have complex electrophysiological properties, however, it is often difficult to determine which properties are the most relevant to neuronal function. By combining current-clamp measurements of electrophysiological properties with multi-variate analysis (hierarchical clustering, principal component analysis), we were able to characterize the postnatal development of substantia nigra dopaminergic neurons' electrical phenotype in an unbiased manner, such that subtle changes in phenotype could be analyzed. We show that the intrinsic electrical phenotype of these neurons follows a non-linear trajectory reaching maturity by postnatal day 14, with two developmental transitions occurring between postnatal days 3–5 and 9–11. This approach also predicted which parameters play a critical role in phenotypic variation, enabling us to determine (using pharmacology, dynamic-clamp) that changes in the leak, sodium and calcium-activated potassium currents are central to these two developmental transitions. This analysis enables an unbiased definition of neuronal type/phenotype that is applicable to a range of research questions.

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 Reduced complement of dopaminergic neurons in the substantia nigra pars compacta of mice with a constitutive “low footprint” genetic knockout of alpha-synuclein

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Valeria V. Goloborshcheva ◽  
Kirill D. Chaprov ◽  
Ekaterina V. Teterina ◽  
Ruslan Ovchinnikov ◽  
Vladimir L. Buchman
Keyword(s):  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Alpha Synuclein ◽  
Substantia Nigra Pars Compacta ◽  
Genetic Knockout

scholarly journals Correct setup of the substantia nigra requires Reelin-mediated fast, laterally-directed migration of dopaminergic neurons

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ankita Ravi Vaswani ◽  
Beatrice Weykopf ◽  
Cathleen Hagemann ◽  
Hans-Ulrich Fried ◽  
Oliver Brüstle ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Cell Morphology ◽  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Molecular Processes ◽  
Direct Role ◽  
Directed Migration ◽  
Tangential Migration ◽  
Dynamic Cell ◽  
Reelin Signaling

Midbrain dopaminergic (mDA) neurons migrate to form the laterally-located substantia nigra pars compacta (SN) and medially-located ventral tegmental area (VTA), but little is known about the underlying cellular and molecular processes. Here we visualize the dynamic cell morphologies of tangentially migrating SN-mDA neurons in 3D and identify two distinct migration modes. Slow migration is the default mode in SN-mDA neurons, while fast, laterally-directed migration occurs infrequently and is strongly associated with bipolar cell morphology. Tangential migration of SN-mDA neurons is altered in absence of Reelin signaling, but it is unclear whether Reelin acts directly on migrating SN-mDA neurons and how it affects their cell morphology and migratory behavior. By specifically inactivating Reelin signaling in mDA neurons we demonstrate its direct role in SN-mDA tangential migration. Reelin promotes laterally-biased movements in mDA neurons during their slow migration mode, stabilizes leading process morphology and increases the probability of fast, laterally-directed migration.

scholarly journals Morphometric analysis of dopaminergic neurons (substantia nigra) in the brain of MPTP-treated alpha-synuclein knockout mice

2021 ◽  
pp. 32-37
Author(s):  
В.В. Голоборщева ◽  
Н.А. Воронина ◽  
Р.К. Овчинников ◽  
В.Г. Кучеряну ◽  
С.Г. Морозов
Keyword(s):  
Substantia Nigra ◽  
Morphometric Analysis ◽  
Knockout Mice ◽  
Dopaminergic Neurons ◽  
Water Solution ◽  
Neuronal Population ◽  
Alpha Synuclein ◽  
Substantia Nigra Pars Compacta ◽  
Mptp Toxicity ◽  
The Brain

Целью данной работы являлась оценка выживаемости популяции зрелых дофаминергических (ДА-ергических) нейронов чёрной субстанции двух альфа-синуклеин нокаутных линий мышей Abel-KO и ΔFlox-KO, а также бессинуклеиновых животных abg-КО в условиях МФТП-токсического моделирования паркинсонического синдрома. Методы исследования: Водный раствор нейротоксина МФТП вводили 3-месячным мышам внутрибрюшинно в дозе 30 мг/кг ежедневно в течение 5 дней по субхроническому протоколу. Через 21 день после последней инъекции МФТП у животных извлекали головной мозг, фиксировали в холодном растворе Карнуа и парафинизировали для последующего приготовления гистологических препаратов на ротационном микротоме Leica RM2265 (Leica Biosystems, Германия). Иммуногистохимическое окрашивание проводили антителами против тирозингидроксилазы (моноклональные антитела мыши, Sigma, разведение 1:2000). Сравнительный морфометрический анализ популяции ДА-ергических нейронов чёрной субстанции выполнен с учётом поправки Аберкромби. Результаты: Установлено, что в условиях дефицита альфа-синуклеина мыши устойчивы к потере ДА-ергических нейронов в компактной части ЧС после введения МФТП. При генетической делеции всех трёх синуклеинов чувствительность ДА-ергических нейронов ЧС к токсическому действию МФТП не отличается от таковой у животных с немодифицированным геномом. Заключение. На основании проведённого морфометрического анализа предполагается, что особенности чувствительности к нейротоксину МФТП у альфа-синуклеин нокаутных линий мышей обусловлены повышением функциональной активности (замещением) бета-синуклеина, оптимизирующего захват ДА синаптическими везикулами. The aim of this study was to assess survival of mature dopaminergic (DAergic) neuronal population in the substantia nigra pars compacta (SNpc) of two alpha-synuclein knockout mice strains (Abel-KO and ΔFlox-KO) and of non-synuclein animals (abg-KO) in MPTP-induced parkinsonism. Material and methods: MPTP water solution was administered to 3-month-old mice intraperitoneally (30 mg/kg daily for 5 days) according to a subchronic protocol. On the 21st day after the last MPTP injection, the brain was excised, fixed in cold Carnoy’s solution and paraffined for the subsequent preparation of histological samples on a Leica RM2265 rotary microtome (Leica Biosystems, Germany). Immunohistochemical staining was performed with antibodies against tyrosine hydroxylase (mouse monoclonal antibodies, Sigma, dilution 1:2000). A comparative morphometric analysis of substantia nigra dopaminergic neurons was performed using the Abercrombie correction. Results: MPTP-treated alpha-synuclein deficient mice were resistant to the loss of DAergic neurons in the SNpc. Genetic deletion of all three synucleins restored the sensitivity of SNpc DAergic neurons to the MPTP toxicity, which did not differ from the sensitivity of wild type animals. Conclusion: Based on the morphometric analysis, it was assumed that the specific features of MPTP sensitivity in alpha-synuclein knockout mice are due to an increased functional activity (substitution) of beta-synuclein, which optimizes the capture of DA by synaptic vesicles.

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