Dopaminergic transmission rapidly and persistently enhances excitability of D1 receptor-expressing striatal projection neurons
Open accessAbstract
Substantia nigra dopamine neurons have been implicated in the initiation and invigoration of movement, presumably through their modulation of striatal projection neuron (SPN) activity. However, the impact of native dopaminergic transmission on SPN excitability has not been directly demonstrated. Using perforated patch-clamp recording, we found that optogenetic stimulation of nigrostriatal dopamine axons rapidly and persistently elevated the excitability of D1 receptor-expressing SPNs (D1-SPNs). The evoked firing of D1-SPNs increased within hundreds of milliseconds of stimulation and remained elevated for ≥ 10 min. Consistent with the negative modulation of depolarization- and Ca 2+-activated K+ currents, dopaminergic transmission accelerated subthreshold depolarization in response to current injection, reduced the latency to fire, and transiently diminished action potential afterhyperpolarization. Persistent modulation was protein kinase A dependent and associated with a reduction in action potential threshold. Together, these data demonstrate that dopaminergic transmission potently increases D1-SPN excitability with a time course that could support subsecond and sustained behavioral control.
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DA release affects postsynaptic cells much more slowly, with about a 500-ms delay, than GABA or glutamate synaptic currents, which last 2-4 ms.
“DA release affects the postsynaptic cell considerably more slowly ($500-ms delay) than the synaptic currents generated by either cotransmitted GABA or glutamate (2-4 ms).115,123”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [123]
Dopamine, GABA, and glutamate released by DANs may elicit prolonged waves of postsynaptic effects, from millisecond excitability changes to tens-of-seconds biochemical signaling and excitability.
“the dopamine, GABA, and glutamate released by DANs may elicit prolonged waves of postsynaptic effects, cascading from the millisecond changes in excitability triggered by ionotropic receptors, to the tens of seconds on biochemical signaling and excitability 109,115,122,123 (Figure 3A).”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [123]
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- Authors
- Lahiri, A. K., & Bevan, M. D.
- Affiliations
- Northwestern University (US)
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- Bevan, Mark D.
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- 277-290.e6
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- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- OSF Preprints (OSF Preprints) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke
- National Cancer Institute
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- dopamine signaling, dopamine D1 receptor, striatal projection neurons, substantia nigra dopamine neurons, nigrostriatal pathway, neuronal excitability, protein kinase A, action potential threshold, afterhyperpolarization, potassium currents, optogenetic stimulation, basal ganglia
- MeSH terms
- Animals, Dopamine, Female, Male, Synaptic Transmission, Neurons, Neostriatum, Receptors, Dopamine D1, Neurotransmitter Agents, Patch-Clamp Techniques, Mice, Electrophysiological Phenomena, Optogenetics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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