Angiotensin II facilitates GABAergic neurotransmission at postsynaptic sites in rat amygdala neurons

Hu, Bo; Qiao, Hu; Cao, Tingyi; Sun, Bo; Luo, Xiao; Jia, Ru; Fan, Yuanyuan; Wang, Nan; Lu, Yi Sheng; Yan, Jiaqi

doi:10.1016/j.neuropharm.2018.02.009

Cited by 5 publications

(2 citation statements)

References 37 publications

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“…Regulation of SNc dopaminergic neurotransmission by SNr GABAergic neurons is well established and contributes to basal nuclei circuit dysfunction ( Deniau et al, 2007 ; Rice et al, 2011 ). Prior investigations show that Ang-II, via activation of AT 1 receptors, modulates GABAergic neurotransmission in the anterior hypothalamus, amygdaloid complex, and the median preoptic nucleus ( Henry et al, 2009 ; Xing et al, 2009 ; Hu et al, 2018 ). Given the strong expression of Ang-II receptors throughout the SN and the predominantly GABAergic control of dopaminergic neurons, Ang-II signaling in SNr GABAergic neurons could potentially modulate intranigral GABAergic and dopaminergic neurotransmission.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin-II Modulates GABAergic Neurotransmission in the Mouse Substantia Nigra

Singh

Vı́gh

Amberg

2021

eNeuro

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Section: Introductionmentioning

confidence: 99%

Angiotensin-II Modulates GABAergic Neurotransmission in the Mouse Substantia Nigra

Singh

Vı́gh

Amberg

2021

eNeuro

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“…Regulation of SNc dopaminergic neurotransmission by SNr GABAergic neurons is well established and contributes to basal ganglia circuit dysfunction (Deniau et al, 2007; Rice et al, 2011). Prior investigations show that Ang-II, via activation of AT 1 receptors, modulates GABAergic neurotransmission in the anterior hypothalamus, amygdala, and the median preoptic nucleus (Henry et al, 2009; Xing et al, 2009; Hu et al, 2018). Given the strong expression of Ang-II receptors throughout the SN and the predominantly GABAergic control of dopaminergic neurons, Ang-II signaling in SNr GABAergic neurons could potentially modulate intranigral GABAergic and dopaminergic neurotransmission.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin-II modulates GABAergic neurotransmission in the mouse substantia nigra

Amberg

Singh

Vı́gh

2021

Preprint

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GABAergic 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.

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Angiotensin II increases the firing activity of pallidal neurons and participates in motor control in rats

2022

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Angiotensin II facilitates GABAergic neurotransmission at postsynaptic sites in rat amygdala neurons

Cited by 5 publications

References 37 publications

Angiotensin-II Modulates GABAergic Neurotransmission in the Mouse Substantia Nigra

Angiotensin-II Modulates GABAergic Neurotransmission in the Mouse Substantia Nigra

Angiotensin-II modulates GABAergic neurotransmission in the mouse substantia nigra

Angiotensin II increases the firing activity of pallidal neurons and participates in motor control in rats

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