Astrocytes mediate the dopaminergic modulation of tonic GABAergic signaling in substantia nigra.
Astrocytes mediate the dopaminergic modulation of tonic GABAergic signaling in substantia nigra.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Chicago, US · Author affiliation
Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.Location evidence
US · Author affiliation · country only
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.Location evidence
San Antonio, US · Author affiliation
Department of Neuroscience, Developmental and Regenerative Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA.Location evidence
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Original 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, GABAA 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 on 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.