4.8 Article

Striatonigrostriatal circuit architecture for disinhibition of dopamine signaling

Journal

CELL REPORTS
Volume 40, Issue 7, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2022.111228

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Funding

  1. NIH K99/R00 award [R00MH109569]
  2. NIH-NINDS T32 award [T32NS041234]

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This study investigates both closed-loop and open-loop striatonigrostriatal circuits using genetic tools. The researchers find strong evidence for closed loops, allowing striatal subregions to regulate their own dopamine release. Evidence for functional synapses in open loops is also found, although these synapses are unable to modulate tonic dopamine neuron firing.
The basal ganglia operate largely in closed parallel loops, including an associative circuit for goal-directed behavior originating from the dorsomedial striatum (DMS) and a somatosensory circuit important for habit formation originating from the dorsolateral striatum (DLS). An exception to this parallel circuit organization has been proposed to explain how information might be transferred between striatal subregions, for example, from the DMS to the DLS during habit formation. The ascending spiral hypothesis proposes that the DMS disinhibits dopamine signaling in the DLS through a tri-synaptic, open-loop striatonigrostriatal circuit. Here, we use transsynaptic and intersectional genetic tools to investigate both closed-and open-loop striatonigrostriatal circuits. We find strong evidence for closed loops, which would allow striatal subregions to regulate their own dopamine release. We also find evidence for functional synapses in open loops. How-ever, these synapses are unable to modulate tonic dopamine neuron firing, questioning the prominence of their role in mediating crosstalk between striatal subregions.

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