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• W3137092013 endingPage "21.2021" @default.
• W3137092013 startingPage "ENEURO.0090" @default.
• W3137092013 abstract "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. Here, 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 (GABAARs) and prolonging the action potential (AP) 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 (RAS) as a functionally relevant neuromodulator in the substantia nigra, thus underscoring a need for additional inquiry." @default.
• W3137092013 created "2021-03-29" @default.
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• W3137092013 date "2021-03-01" @default.
• W3137092013 modified "2023-09-26" @default.
• W3137092013 title "Angiotensin-II Modulates GABAergic Neurotransmission in the Mouse Substantia Nigra" @default.
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• W3137092013 doi "https://doi.org/10.1523/eneuro.0090-21.2021" @default.
• W3137092013 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8174047" @default.
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