Astrocytes modulate extracellular neurotransmitter levels and excitatory neurotransmission in dorsolateral striatum via dopamine D2 receptor signaling
Open accessAbstract
Astrocytes provide structural and metabolic support of neuronal tissue, but may also be involved in shaping synaptic output. To further define the role of striatal astrocytes in modulating neurotransmission we performed in vivo microdialysis and ex vivo slice electrophysiology combined with metabolic, chemogenetic, and pharmacological approaches. Microdialysis recordings revealed that intrastriatal perfusion of the metabolic uncoupler fluorocitrate (FC) produced a robust increase in extracellular glutamate levels, with a parallel and progressive decline in glutamine. In addition, FC significantly increased the microdialysate concentrations of dopamine and taurine, but did not modulate the extracellular levels of glycine or serine. Despite the increase in glutamate levels, ex vivo electrophysiology demonstrated a reduced excitability of striatal neurons in response to FC. The decrease in evoked potentials was accompanied by an increased paired pulse ratio, and a reduced frequency of spontaneous excitatory postsynaptic currents, suggesting that FC depresses striatal output by reducing the probability of transmitter release. The effect by FC was mimicked by chemogenetic inhibition of astrocytes using G i-coupled designer receptors exclusively activated by designer drugs (DREADDs) targeting GFAP, and by the glial glutamate transporter inhibitor TFB-TBOA. Both FC- and TFB-TBOA-mediated synaptic depression were inhibited in brain slices pre-treated with the dopamine D2 receptor antagonist sulpiride, but insensitive to agents acting on presynaptic glutamatergic autoreceptors, NMDA receptors, gap junction coupling, cannabinoid 1 receptors, µ-opioid receptors, P2 receptors or GABA A receptors. In conclusion, our data collectively support a role for astrocytes in modulating striatal neurotransmission and suggest that reduced transmission after astrocytic inhibition involves dopamine.
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An increase in DA signaling brought on by compromised astrocyte activity may induce a long-lasting change in striatal neurotransmission since DA signaling is crucial for both structural and synaptic plasticity.
“An increase in DA signaling brought on by compromised astrocyte activity may induce a long-lasting change in striatal neurotransmission 80 since DA signaling is crucial for both structural and synaptic plasticity. 82”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [80]
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Major depressive disorder: hypothesis, mechanism, prevention and treatment
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“81 An increase in DA signaling brought on by compromised astrocyte activity may induce a long-lasting change in striatal neurotransmission 80 since DA signaling is crucial for both structural and synaptic plasticity.”
Background
- Authors
- Adermark, L., Lagström, O., Loftén, A., Licheri, V., Havenäng, A., Loi, E. A., Stomberg, R., Söderpalm, B., Domi, A., & Ericson, M.
- Affiliations
- University of Gothenburg (SE)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Adermark, Louise
- Venue
- Neuropsychopharmacology
- Published
- 2021-11-22
- Volume
- 47
- Issue
- 8
- Pages
- 1493-1502
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC9206030
- OpenAlex
- W3215653006
- Cited by
- 51
- References
- 86
- Citations by year
- 2026: 14 · 2025: 9 · 2024: 18 · 2023: 6 · 2022: 3
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vetenskapsrådet (2018‐02814, 2020-01346, 2020-02105)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- astrocytes, dorsolateral striatum, dopamine D2 receptor, excitatory neurotransmission, extracellular glutamate, fluorocitrate, synaptic depression, neurotransmitter release probability, glial fibrillary acidic protein, sulpiride, astrocyte-neuron interaction, glutamate transporters
- MeSH terms
- Astrocytes, Dopamine, Synaptic Transmission, Receptors, Dopamine D2, Glutamic Acid, Dopamine D2 Receptor Antagonists
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