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 Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular Axons

2021 ◽  
Vol 9 ◽  
Author(s):  
Verónica Company ◽  
Abraham Andreu-Cervera ◽  
M. Pilar Madrigal ◽  
Belén Andrés ◽  
Francisca Almagro-García ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Dopaminergic Neurons ◽  
Functional Organization ◽  
Substantia Nigra Pars Compacta ◽  
Fasciculus Retroflexus ◽  
Ventral Tegmental

The fasciculus retroflexus is an important fascicle that mediates reward-related behaviors and is associated with different psychiatric diseases. It is the main habenular efference and constitutes a link between forebrain regions, the midbrain, and the rostral hindbrain. The proper functional organization of habenular circuitry requires complex molecular programs to control the wiring of the habenula during development. However, the mechanisms guiding the habenular axons toward their targets remain mostly unknown. Here, we demonstrate the role of the mesodiencephalic dopaminergic neurons (substantia nigra pars compacta and ventral tegmental area) as an intermediate target for the correct medial habenular axons navigation along the anteroposterior axis. These neuronal populations are distributed along the anteroposterior trajectory of these axons in the mesodiencephalic basal plate. Using in vitro and in vivo experiments, we determined that this navigation is the result of netrin 1 attraction generated by the mesodiencephalic dopaminergic neurons. This attraction is mediated by the receptor deleted in colorectal cancer (DCC), which is strongly expressed in the medial habenular axons. The increment in our knowledge on the fasciculus retroflexus trajectory guidance mechanisms opens the possibility of analyzing if its alteration in mental health patients could account for some of their symptoms.

scholarly journals Protective effect of Curcumin against rotenone-induced Substantia nigra pars compacta neuronal dysfunction

2021 ◽  
Author(s):  
Lilit Vahan Darbinyan ◽  
Lilia Eduard Hambardzumyan ◽  
Larisa Paylak Manukyan ◽  
Karen Vazgen Simonyan ◽  
Carlos Augusto Carvalho de Vasconcelos ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Therapeutic Agent ◽  
Male Rats ◽  
Substantia Nigra Pars Compacta ◽  
Nissl Staining ◽  
Histological Changes ◽  
Naturally Occurring ◽  
The Brain

Abstract Rotenone is involved in the degeneration of dopaminergic neurons, and curcumin may prevent or effectively slow the progression of Parkinson disease (PD). Previous research has shown that the naturally occurring phenolic compound curcumin can reduce inflammation and oxidation, making it a potential therapeutic agent for neurodegenerative diseases. The present study involves investigation of rotenone induced histological changes in the brain areas, hippocampus using Nissl staining after 35 day of subcutaneous injection administration of rotenone in adult male rats. In this study, we investigated whether curcumin protects against rotenone-induced dopaminergic neurotoxicity in a rat model by in vivo electrical recording from Substantia nigra pars compacta (SNc). Curcumin treatment significantly improved electrical activity of neurons in the SNc of rotenone-induced PD model rats. The pattern of histological alterations corresponds with electrophysiological manifestations.

scholarly journals Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway

2020 ◽  
Author(s):  
Ya-Dong Li ◽  
Yan-Jia Luo ◽  
Wei Xu ◽  
Jing Ge ◽  
Yoan Cherasse ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Gabaergic Neurons ◽  
Population Activity ◽  
Lateral Habenula ◽  
Optogenetic Stimulation ◽  
Ventral Tegmental ◽  
Stimulation Of

Abstract The ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits of the VP in the control of wakefulness remain poorly understood. In the present study, we sought to elucidate the specific role of VP GABAergic neurons in controlling sleep–wake behaviors in mice. Fiber photometry revealed that the population activity of VP GABAergic neurons was increased during physiological transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep. Moreover, chemogenetic and optogenetic manipulations were leveraged to investigate a potential causal role of VP GABAergic neurons in initiating and/or maintaining arousal. In vivo optogenetic stimulation of VP GABAergic neurons innervating the ventral tegmental area (VTA) strongly promoted arousal via disinhibition of VTA dopaminergic neurons. Functional in vitro mapping revealed that VP GABAergic neurons, in principle, inhibited VTA GABAergic neurons but also inhibited VTA dopaminergic neurons. In addition, optogenetic stimulation of terminals of VP GABAergic neurons revealed that they promoted arousal by innervating the lateral hypothalamus, but not the mediodorsal thalamus or lateral habenula. The increased wakefulness chemogenetically evoked by VP GABAergic neuronal activation was completely abolished by pretreatment with dopaminergic D1 and D2/D3 receptor antagonists. Furthermore, activation of VP GABAergic neurons increased exploration time in both the open-field and light–dark box tests but did not modulate depression-like behaviors or food intake. Finally, chemogenetic inhibition of VP GABAergic neurons decreased arousal. Taken together, our findings indicate that VP GABAergic neurons are essential for arousal related to motivation.

Muscarine Reduces Calcium-Dependent Electrical Activity in Substantia Nigra Dopaminergic Neurons

2001 ◽  
Vol 86 (6) ◽  
pp. 2966-2972 ◽  
Author(s):  
Reese S. Scroggs ◽  
Carla G. Cardenas ◽  
Joseph A. Whittaker ◽  
Stephen T. Kitai
Keyword(s):  
Substantia Nigra ◽  
Electrical Activity ◽  
Dopaminergic Neurons ◽  
Brain Slices ◽  
Oscillatory Potentials ◽  
Substantia Nigra Pars Compacta ◽  
Pontine Nucleus ◽  
Calcium Dependent ◽  
The Brain

The effect of muscarine on Ca2+ dependent electrical activity was studied in dopamine (DA) neurons located in the substantia nigra pars compacta (SNc) in brain slices from young rats, using sharp electrodes. In most DA neurons tested, muscarine (50 μM) reduced the amplitude of spontaneous oscillatory potentials and evoked Ca2+-dependent potentials recorded in the presence of TTX. Muscarine also reduced the amplitude of the slow afterhyperpolarization (sAHP) following action potentials in most DA neurons. These data suggest that muscarine reduces Ca2+ entry in SNc DA neurons. The reduction of the amplitude of the sAHP by muscarine in DA neurons may facilitate bursting initiated by glutamatergic input by increasing the frequency at which DA neurons can fire. The reduction of the sAHP via activation of muscarinic receptors in vivo may provide a mechanism whereby cholinergic inputs to DA neurons from the tegmental peduncular pontine nucleus could modulate dopamine release at dopaminergic targets in the brain.

Subthalamic Stimulation-Induced Synaptic Responses in Substantia Nigra Pars Compacta Dopaminergic Neurons In Vitro

1999 ◽  
Vol 82 (2) ◽  
pp. 925-933 ◽  
Author(s):  
Yuji Iribe ◽  
Kevin Moore ◽  
Kevin C. H. Pang ◽  
James M. Tepper
Keyword(s):  
Substantia Nigra ◽  
Glutamate Receptor ◽  
Dopaminergic Neurons ◽  
Reversal Potential ◽  
Substantia Nigra Pars Compacta ◽  
Inhibitory Effects ◽  
Synaptic Potentials ◽  
Stimulation Of ◽  
Synaptic Responses

The subthalamic nucleus (STN) is one of the principal sources of excitatory glutamatergic input to dopaminergic neurons of the substantia nigra, yet stimulation of the STN produces both excitatory and inhibitory effects on nigral dopaminergic neurons recorded extracellularly in vivo. The present experiments were designed to determine the sources of the excitatory and inhibitory effects. Synaptic potentials were recorded intracellularly from substantia nigra pars compacta dopaminergic neurons in parasagittal slices in response to stimulation of the STN. Synaptic potentials were analyzed for onset latency, amplitude, duration, and reversal potential in the presence and absence of GABA and glutamate receptor antagonists. STN-evoked depolarizing synaptic responses in dopaminergic neurons reversed at approximately −31 mV, intermediate between the expected reversal potential for an excitatory and an inhibitory postsynaptic potential (EPSP and IPSP). Blockade of GABAA receptors with bicuculline caused a positive shift in the reversal potential to near 0 mV, suggesting that STN stimulation evoked a near simultaneous EPSP and IPSP. Both synaptic responses were blocked by application of the glutamate receptor antagonist, 6-cyano-7-nitroquinoxalene-2,3-dione. The confounding influence of inhibitory fibers of passage from globus pallidus and/or striatum by STN stimulation was eliminated by unilaterally transecting striatonigral and pallidonigral fibers 3 days before recording. The reversal potential of STN-evoked synaptic responses in dopaminergic neurons in slices from transected animals was approximately −30 mV. Bath application of bicuculline shifted the reversal potential to ∼5 mV as it did in intact animals, suggesting that the source of the IPSP was within substantia nigra. These data indicate that electrical stimulation of the STN elicits a mixed EPSP-IPSP in nigral dopaminergic neurons due to the coactivation of an excitatory monosynaptic and an inhibitory polysynaptic connection between the STN and the dopaminergic neurons of substantia nigra pars compacta. The EPSP arises from a direct monosynaptic excitatory glutamatergic input from the STN. The IPSP arises polysynaptically, most likely through STN-evoked excitation of GABAergic neurons in substantia nigra pars reticulata, which produces feed-forward GABAA-mediated inhibition of dopaminergic neurons through inhibitory intranigral axon collaterals.

scholarly journals Characterization of substantia nigra neurogenesis in homeostasis and dopaminergic degeneration: beneficial effects of the microneurotrophin BNN-20

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Theodora Mourtzi ◽  
Dimitrios Dimitrakopoulos ◽  
Dimitrios Kakogiannis ◽  
Charalampos Salodimitris ◽  
Konstantinos Botsakis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Substantia Nigra ◽  
Mouse Model ◽  
Dopaminergic Neurons ◽  
Stem Cell Niche ◽  
Substantia Nigra Pars Compacta ◽  
Dopaminergic Cell ◽  
Cell Niche

Abstract Background Loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) underlines much of the pathology of Parkinson’s disease (PD), but the existence of an endogenous neurogenic system that could be targeted as a therapeutic strategy has been controversial. BNN-20 is a synthetic, BDNF-mimicking, microneurotrophin that we previously showed to exhibit a pleiotropic neuroprotective effect on the dopaminergic neurons of the SNpc in the “weaver” mouse model of PD. Here, we assessed its potential effects on neurogenesis. Methods We quantified total numbers of dopaminergic neurons in the SNpc of wild-type and “weaver” mice, with or without administration of BNN-20, and we employed BrdU labelling and intracerebroventricular injections of DiI to evaluate the existence of dopaminergic neurogenesis in the SNpc and to assess the origin of newborn dopaminergic neurons. The in vivo experiments were complemented by in vitro proliferation/differentiation assays of adult neural stem cells (NSCs) isolated from the substantia nigra and the subependymal zone (SEZ) stem cell niche to further characterize the effects of BNN-20. Results Our analysis revealed the existence of a low-rate turnover of dopaminergic neurons in the normal SNpc and showed, using three independent lines of experiments (stereologic cell counts, BrdU and DiI tracing), that the administration of BNN-20 leads to increased neurogenesis in the SNpc and to partial reversal of dopaminergic cell loss. The newly born dopaminergic neurons, that are partially originated from the SEZ, follow the typical nigral maturation pathway, expressing the transcription factor FoxA2. Importantly, the pro-cytogenic effects of BNN-20 were very strong in the SNpc, but were absent in other brain areas such as the cortex or the stem cell niche of the hippocampus. Moreover, although the in vitro assays showed that BNN-20 enhances the differentiation of NSCs towards glia and neurons, its in vivo administration stimulated only neurogenesis. Conclusions Our results demonstrate the existence of a neurogenic system in the SNpc that can be manipulated in order to regenerate the depleted dopaminergic cell population in the “weaver” PD mouse model. Microneurotrophin BNN-20 emerges as an excellent candidate for future PD cell replacement therapies, due to its area-specific, pro-neurogenic effects.

scholarly journals To be or not to be pink(1): contradictory findings in an animal model for Parkinson’s disease

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Ria de Haas ◽  
Lisa C M W Heltzel ◽  
Denise Tax ◽  
Petra van den Broek ◽  
Hilbert Steenbreker ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
In Vivo Microdialysis ◽  
Substantia Nigra Pars Compacta ◽  
Laboratory Animals ◽  
Motor Deficits

Abstract The PTEN-induced putative kinase 1 knockout rat (Pink1−/−) is marketed as an established model for Parkinson’s disease, characterized by development of motor deficits and progressive degeneration of half the dopaminergic neurons in the substantia nigra pars compacta by 8 months of age. In this study, we address our concerns about the reproducibility of the Pink1−/− rat model. We evaluated behavioural function, number of substantia nigra dopaminergic neurons and extracellular striatal dopamine concentrations by in vivo microdialysis. Strikingly, we and others failed to observe any loss of dopaminergic neurons in 8-month-old male Pink1−/− rats. To understand this variability, we compared key experimental parameters from the different studies and provide explanations for contradictory findings. Although Pink1−/− rats developed behavioural deficits, these could not be attributed to nigrostriatal degeneration as there was no loss of dopaminergic neurons in the substantia nigra and no changes in neurotransmitter levels in the striatum. To maximize the benefit of Parkinson’s disease research and limit the unnecessary use of laboratory animals, it is essential that the research community is aware of the limits of this animal model. Additional research is needed to identify reasons for inconsistency between Pink1−/− rat colonies and why degeneration in the substantia nigra is not consistent.

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