Exploring a Dopamine Neuron and Striatal Circuit

Strahinja Stojanovic, Christopher Joseph Knowlton, Richard Egger-Mackrodt, Johanna Mankel, Josef Shin et al.

(see article e0361252025)

Dopamine neurons and striatal circuits support movement control and reward learning and are implicated in Parkinson's disease and schizophrenia. Thus, exploring pathways from dopamine neurons to distinct striatal regions may shed light on impairments in disease states. Substantia nigra (SN) dopamine neurons targeting the dorsolateral striatum (DLS) have fast dynamics, which may relate to the importance of this pathway for vigorous movements. In this issue, Stojanovic et al. explored mechanisms for the quick dynamics of this projection. Using mice, the authors unveiled a unique biophysical profile for these SN neurons that enables rapid rebound bursting. Whole-cell patch-clamp electrophysiology and projection-specific computational models revealed the roles of specific channels in this rebound bursting. Two channels (voltage-gated calcium and calcium-activated potassium) on SN neurons projecting to the DLS controlled rapid rebound firing. A second set of channels (voltage-gated potassium and hyperpolarization-activated) regulated the timing of this rebound. In contrast, another channel (GIRK) interacted with inhibitory dopamine (D2) and GABA (GABAB) receptors to prevent rebound bursting. In vivo patch-clamp recordings and computational in vivo models confirmed that these rebound properties also exist in the intact brain. According to the authors, these findings advance understanding of the mechanisms that enable the rapid dynamics of this SN-DLS pathway.

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Confocal images of retrogradely red bead (RB)-traced (top left, red; bottom right, black) dopamine neurons costained for tyrosine hydroxylase (TH, blue) and an aldehyde dehydrogenase 1 marker (Aldh1a1, green). See Stojanovic et al. for more information.