scholarly journals Angiotensin-II modulates GABAergic neurotransmission in the mouse substantia nigra

2021 ◽  
Author(s):  
Maibam R. Singh ◽  
Jozsef Vigh ◽  
Gregory C. Amberg
Keyword(s):  
Angiotensin Ii ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Neuronal Activity ◽  
Dopaminergic Neurons ◽  
Gabaergic Neurons ◽  
Inhibitory Input ◽  
Ang Ii ◽  
Signaling Mechanism ◽  
Gabaergic Neurotransmission

ABSTRACTGABAergic projections neurons of the substantia nigra reticulata (SNr), through an extensive network of dendritic arbors and axon collaterals, provide robust inhibitory input to neighboring dopaminergic neurons in the substantia nigra compacta (SNc). Angiotensin-II (Ang-II) receptor signaling increases SNc dopaminergic neuronal sensitivity to insult, thus rendering these cells susceptible to dysfunction and destruction. However, the mechanisms by which Ang-II regulates SNc dopaminergic neuronal activity are unclear. Given the complex relationship between SN dopaminergic and GABAergic neurons, we hypothesized that Ang-II could regulate SNc dopaminergic neuronal activity directly and indirectly by modulating SNr GABAergic neurotransmission. Herein, using transgenic mice, slice electrophysiology, and optogenetics, we provide evidence of an AT1 receptor-mediated signaling mechanism in SNr GABAergic neurons where Ang-II suppresses electrically-evoked neuronal output by facilitating postsynaptic GABAA receptors and prolonging the action potential duration. Unexpectedly, Ang-II had no discernable effects on the electrical properties of SNc dopaminergic neurons. Also, and indicating a nonlinear relationship between electrical activity and neuronal output, following phasic photoactivation of SNr GABAergic neurons, Ang-II paradoxically enhanced the feedforward inhibitory input to SNc dopaminergic neurons. In sum, our observations describe an increasingly complex and heterogeneous response of the SN to Ang-II by revealing cell-specific responses and nonlinear effects on intranigral GABAergic neurotransmission. Our data further implicate the renin-angiotensin-system as a functionally relevant neuromodulator in the basal ganglia, thus underscoring a need for additional inquiry.SIGNIFICANCE STATEMENTAngiotensin II (Ang-II) promotes dopamine release in the striatum and, in the substantia nigra compacta (SNc), exacerbates dopaminergic cell loss in animal models of Parkinson’s disease. Despite a potential association with Parkinson’s disease, the effects of Ang-II on neuronal activity in the basal ganglia is unknown. Here we describe a novel AT1 receptor-dependent signaling mechanism in GABAergic projection neurons of the SN reticulata (SNr), a major inhibitory regulator of SNc dopaminergic neurons. Specifically, Ang-II suppresses SNr GABAergic neuronal activity, subsequently altering GABAergic modulation of SNc dopaminergic neurons in a nonlinear fashion. Altogether, our data provide the first indication of Ang-II-dependent modulation of GABAergic neurotransmission in the SN, which could impact output from the basal ganglia in health and disease.

Effects of angiotensin II on proximal tubular cells stably transfected with the c-mas oncogene

1992 ◽  
Vol 263 (5) ◽  
pp. F931-F938 ◽  
Author(s):  
G. Wolf ◽  
E. G. Neilson
Keyword(s):  
Angiotensin Ii ◽  
De Novo ◽  
Cell Phenotype ◽  
Scatchard Analysis ◽  
Tubular Epithelium ◽  
Ang Ii ◽  
Protein Signaling ◽  
Signaling Mechanism ◽  
Cellular Hypertrophy ◽  
Proximal Tubular

Angiotensin II (ANG II) normally induces cellular hypertrophy in proximal tubular epithelium by engaging receptor systems that use a G-protein-signaling mechanism. The c-mas oncogene also encodes part of a superfamily of vasoactive peptide receptor-like moieties that couple to G proteins. To determine whether the stable expression of the c-mas gene might alter or modify the induction of cellular hypertrophy by ANG II in tubular epithelium, a rat c-mas cDNA was cloned into the pSV2 expression vector for use in cell transfection. Scatchard analysis of ANG II binding revealed no significant differences in ANG II receptor number or in the dissociation constant between pSV2mas-transfected or wild-type MCT cells, but rather an increase in the number of receptors not replaceable by known inhibitors. ANG II also induced proliferation in pSV2mas-transfected MCT cells that was not blocked by conventional inhibitors and increased intracellular levels of inositol trisphosphate. ANG II, furthermore, did not increase de novo protein synthesis in pSV2-transfected MCT cells and failed to lower their intracellular concentration of adenosine 3',5'-cyclic monophosphate, both expected parameters of cellular hypertrophy. Our findings demonstrate that expression of c-mas in tubular epithelium can modulate tubular cell phenotype toward proliferation rather than hypertrophy. This effect is likely mediated by a reshuffling of the heterogeneity of ANG II receptors on the cell surface, or perhaps by the emergence of a new ANG II receptor, followed by alterations in the process of signal transduction.

scholarly journals Autophagin-3 (ATG4C) is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Differentially Expressed ◽  
Gene Encoding ◽  
Microarray Datasets

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published microarray datasets (2, 3) to identify genes whose expression was most different in the substantial nigra of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding autophagin-3 (ATG4C) in the substantia nigra of patients with PD.

Angiotensin II receptor binding associated with nigrostriatal dopaminergic neurons in human basal ganglia

1992 ◽  
Vol 32 (3) ◽  
pp. 339-344 ◽  
Author(s):  
Andrew M. Allen ◽  
Duncan P. MacGregor ◽  
Siew Y. Chai ◽  
Geoffrey A. Donnan ◽  
Stanislav Kaczmarczyk ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Basal Ganglia ◽  
Receptor Binding ◽  
Dopaminergic Neurons ◽  
Angiotensin Ii Receptor

scholarly journals LINC00643 is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Differentially Expressed ◽  
Gene Encoding ◽  
Non Coding Rna ◽  
Microarray Datasets

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published and public microarray datasets (2, 3) to identify genes whose expression was most different in the substantial nigra of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding the long intergenic non-coding RNA LINC00643 in the substantia nigra of patients with PD.

scholarly journals CDK6 is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Differentially Expressed ◽  
Cyclin Dependent Kinase ◽  
Gene Encoding

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published and public microarray (2, 3) datasets to identify genes whose expression was most different in the brains of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding the cyclin-dependent kinase CDK6 in the substantia nigra of patients with PD.

scholarly journals ID2 is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factor ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Differentially Expressed ◽  
Gene Encoding

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published and public microarray (2, 3) datasets to identify genes whose expression was most different in the brains of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding the transcription factor ID2 in the substantia nigra of patients with PD.

scholarly journals C18ORF54 is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Open Reading Frame ◽  
Differentially Expressed ◽  
Reading Frame ◽  
Microarray Datasets

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published and public microarray datasets (2, 3, 4) to identify genes whose expression was most different in the substantial nigra of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of open reading frame 18 on chromosome 54 (C18ORF54) in the substantia nigra of patients with PD.

scholarly journals Arousal-State Dependent Alterations in VTA-GABAergic Neural Activity

2019 ◽  
Author(s):  
Ada Eban-Rothschild ◽  
Jeremy C. Borniger ◽  
Gideon Rothschild ◽  
William J. Giardino ◽  
Joshua G. Morrow ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Neuronal Activity ◽  
Rem Sleep ◽  
Neural Activity ◽  
Dopaminergic Neurons ◽  
Nrem Sleep ◽  
Gabaergic Neurons ◽  
Population Activity ◽  
Arousal State ◽  
State Dependent

AbstractDecades of research have implicated the ventral tegmental area (VTA) in motivation, reinforcement learning and reward processing. We and others recently demonstrated that it also serves as an important node in sleep/wake circuitry. Specifically, VTA-dopaminergic neuron activation is sufficient to drive wakefulness and necessary for the maintenance of wakefulness. However, the role of VTA gamma-aminobutyric acid (GABA)-expressing neurons in arousal regulation is not fully understood. It is still unclear whether VTA-GABAergic neurons predictably alter their firing properties across arousal states, what is the nature of interactions between VTA-GABAergic activity and cortical neural oscillations, and how activity in VTA-GABAergic neurons relates to VTA-dopaminergic neurons in the context of sleep/wake regulation. To address these questions, we simultaneously recorded population activity from VTA-GABAergic or VTA-dopaminergic neurons and EEG/EMG signals during spontaneous sleep/wake states and in the presence of salient stimuli in freely-behaving male mice. We observed that VTA-GABAergic neurons exhibit robust arousal-state-dependent alterations in population activity, with high activity and calcium transients during wakefulness and rapid-eye-movement (REM) sleep compared to non-REM (NREM) sleep. During wakefulness, population activity of VTA-GABAergic neurons, but not VTA-dopaminergic neurons, was positively correlated with EEG gamma power and negatively correlated with EEG theta power. During NREM sleep, population activity in both VTA-GABAergic and VTA-dopaminergic neurons negatively correlated with delta, theta, and sigma EEG power bands. Salient stimuli, with both positive and negative valence, activated VTA-GABAergic neurons. The strongest activation was observed for social stimuli irrespective of valence. Together, our data indicate that VTA-GABAergic neurons, like their dopaminergic counterparts, drastically alter their activity across sleep-wake states. Changes in their activity predicts cortical oscillatory patterns reflected in the EEG, which are distinct from EEG spectra associated with dopaminergic neural activity.Statement of SignificanceLittle is known about how ventral tegmental area (VTA) neural ensembles couple arousal to motivated behaviors. Using cell-type specific genetic tools, we investigated the population activity of GABAergic and dopaminergic neurons within the VTA across sleep/wake states and in the presence of salient stimuli. We demonstrate that coordinated neural activity within VTA-GABAergic neurons peaks during wakefulness and REM sleep. Furthermore, neuronal activity in VTA-GABAergic neurons is correlated with high frequency, low amplitude cortical oscillations during waking, but negatively correlated with high amplitude slower frequency oscillations during NREM sleep. Our results demonstrate that VTA-GABAergic neuronal activity is tightly linked to cortical arousal and highlight this population as a potential important node in sleep/wake regulation.

scholarly journals Neurotransmitters in the Basal Ganglia

1984 ◽  
Vol 11 (S1) ◽  
pp. 89-99 ◽  
Author(s):  
Edith G. McGeer ◽  
William A. Staines ◽  
Patrick L. McGeer
Keyword(s):  
Cell Death ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Globus Pallidus ◽  
Dopaminergic Neurons ◽  
Pivotal Role ◽  
Substantia Nigra Pars Reticulata ◽  
Caudate Putamen ◽  
Motor Pathways ◽  
Stimulation Of

ABSTRACTThe literature is reviewed on the afferents and efferents of the caudate/putamen, globus pallidus and substantia nigra, and on the neurotransmitters occurring in the various tracts. Emphasis is placed upon the diverse roles played by GABA and glutamate as transmitters in motor pathways and upon the probability that the substantia nigra pars reticulata plays a pivotal role in the output of the basal ganglia. Excessive stimulation of the projection from the pedunculopontine tegmental area to the substantia nigra is shown to cause destruction of dopaminergic neurons in the latter nucleus, suggesting another possible mechanism for cell death in Parkinson’s disease.

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