Astrocytes mediate the dopaminergic modulation of tonic GABAergic signaling in substantia nigra
Year: 2024
Type: preprint
Abstract: Recent studies have implicated dopaminergic signaling within the substantia nigra pars reticulata (SNr) in the emergence of Parkinsonian motor deficits. To better understand the mechanisms underlying this dependence, the ability of dopamine to modulate SNr neuron activity was studied in ex vivo mouse brain slices. In addition to presynaptically inhibiting phasic GABA release, D2 dopamine receptor (D2R) signaling unexpectedly suppressed a tonic, GABA A receptor-mediated inhibition of SNr neuron spiking. Our studies demonstrated that this tonic modulation was largely mediated by GAT-1-dependent GABA release from ALDH1A1-expressing dopaminergic neurons. In contrast, the ability of D2R agonists to disinhibit SNr neurons depended upon D2R-expressing astrocytes and stimulation of GAT-3 uptake of GABA from the extracellular space. In addition to underscoring the importance of dendritically released dopamine in modulating synaptic transmission, our studies demonstrate that dopaminergic modulation of astrocytes plays a key role in modulating SNr circuits and motor behavior. Teaser SNc dopaminergic neurons and astrocytes regulate tonic GABAergic inhibition of SNr neurons.
Authors: DeNard V Simmons, Oscar Andrés Moreno-Ramos, Divya D.A. Raj, Konstantin Kaganovsky, Arin Pamukcu, Nora Vrieler, Tatiana Tkatch, Zhong Xie, Ana Isabel Silva de Sousa, Enrico Zampese, Jun Ding, Rajeshwar Awatramani, Charles J. Wilson, D. James Surmeier
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: G1969326112, G4710536820
OpenAlex ID: W4393338914