ePoster

Shuttle of dopamine through astroglial networks regulates prefrontal neurotransmission

Xia Li, Wenli Niu, Sambre Mach, Juliette Royer, Olga Chaikovska, Paola Bezzi, Micaela Galante *, Glenn Dallérac *
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Xia Li, Wenli Niu, Sambre Mach, Juliette Royer, Olga Chaikovska, Paola Bezzi, Micaela Galante *, Glenn Dallérac *

Abstract

The prefrontal cortex plays a crucial role in cognitive functions such as decision making, planning, and working memory. It is subjected to strong monoaminergic neuromodulation, particularly by dopamine from the VTA. While dopamine innervations in the prefrontal cortex are sparse, recent research indicates that the vesicular dopamine transporter VMAT2 in astrocytes contributes to dopaminergic homeostasis in the prefrontal cortex. Here we hypothesized that astrocytes could provide a shuttle mechanism through which appropriate tonic levels of dopamine would be redistributed across the prefrontal neuronal network via astroglial release. To test this hypothesis, we used ex vivo imaging of dopamine, detected via the genetically encoded fluorescent sensor GRABDA in acute prefrontal slices under 2-photons microscopy. Our results show that the sensor can detect calcium-dependent spontaneous release of dopamine. We further find that the latter is not impinged by blockade of action potentials with TTX while it is enhanced by chemogenetic or pharmacological activation of astrocytes. Strikingly, spontaneous liberation of dopamine was severely impaired in mice knocked-down for astroglial VMAT2. We next investigated, using electrophysiological recordings, whether astroglial dopamine can influence prefrontal synaptic transmission and neuronal excitability. Our results indicate that intracellular diffusion of dopamine in the astrocytic network upregulates synaptic transmission. Such regulation is however absent in mouse lines lacking astrocytic gap junctions and VMAT2. Finally, our findings suggest that neuronal excitability is minimally affected by astrocytic dopamine. Overall, these results align with the view that astroglial network shuttling and release of dopamine modulates neuronal activities in the PFC.

Unique ID: fens-24/shuttle-dopamine-through-astroglial-4a2ef728