Document Type
Article
Publication Date
10-29-2025
Publication Title
The Journal of Neuroscience
Abstract
Dopamine (DA) midbrain neurons are involved in a wide array of key brain functions including movement control and reward-based learning. They are also critical for major brain disorders such as Parkinson's disease or schizophrenia. DA neurons projecting to distinct striatal territories are diverse with regard to their molecular makeup and cellular physiology, which are likely to contribute to the observed differences in temporal DA dynamics. Among these regions, the dorsolateral striatum (DLS) displays the fastest DA dynamics, which might control the moment-to-moment vigor and variability of voluntary movements. However, the underlying mechanisms for these DLS-specific fast DA fluctuations are unresolved. Here, we show that DLS-projecting DA neurons in the substantia nigra (SN) possess a unique biophysical profile allowing immediate 10-fold accelerations in discharge frequency via rebound bursting. By using a combination of in vitro patch-clamp recordings in projection-defined DA SN subpopulations from adult male mice and developing matching projection-specific computational models, we demonstrate that a strong interaction of Ca3 and SK channels specific for DLS-projecting Aldh1a1-positive DA SN (DLS-DA) neurons controls the gain of fast rebound bursting, while K4 and HCN channels mediate timing of rebound excitability. In addition, GIRK channels activated by D2 and GABA receptors prevent rebound bursting in these DLS-DA neurons. Furthermore, our in vivo patch-clamp recordings and matching in vivo computational models provide evidence that these unique rebound properties might be preserved in the intact brain, where they might endow specific computational properties well suited for the generation of fast DA dynamics present in DLS.
PubMed ID
41006064
Volume
45
Issue
44
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Stojanovic, Strahinja; Knowlton, Christopher J.; Egger-Mackrodt, Richard; Mankel, Johanna; Shin, Josef; Lammel, Stephan; Canavier, Carmen C.; and Roeper, Jochen, "Rebound Bursting Selectively Enables Fast Dynamics in Dopamine Midbrain Neurons Projecting to the Dorsolateral Striatum" (2025). School of Graduate Studies Faculty Publications. 450.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/450
10.1523/JNEUROSCI.0361-25.2025
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