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Behavioral encoding across timescales by region-specific dopamine dynamics.

Søren H Jørgensen1, Aske L Ejdrup1, Matthew D Lycas1

  • 1Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.

Proceedings of the National Academy of Sciences of the United States of America
|February 7, 2023
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Summary

Dopamine release in the dorsal striatum (DS) and ventral striatum (VS) coordinates distinct behaviors. Rapid DS signals guide action sequencing, while slower VS signals initiate and sustain actions, revealing coordinated striatal dopamine dynamics.

Keywords:
cocainedopamine releasedopamine sensorsmachine learningmouse behavior

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Area of Science:

  • Neuroscience
  • Behavioral Science
  • Neuropharmacology

Background:

  • The dorsal striatum (DS) and ventral striatum (VS) are key dopamine-innervated regions involved in motor control and reward processing.
  • Understanding the precise coupling between dopamine release dynamics and specific behaviors across these striatal subregions remains a significant challenge.

Purpose of the Study:

  • To decode dopamine release dynamics in the DS and VS during unconstrained exploratory behavior in mice.
  • To investigate the relationship between striatal dopamine signaling across different temporal scales and discrete behavioral motifs.
  • To examine the impact of dopamine system disruption on action sequencing and DS-VS coordination.

Main Methods:

  • Utilized the dLight1.3b dopamine sensor and multiregion fiber photometry in mice.
  • Employed machine learning-based analysis to decode dopamine dynamics during self-paced exploratory behavior.
  • Administered cocaine to disrupt dopamine dynamics and assess behavioral consequences.

Main Results:

  • Observed distinct dopamine release patterns: rapidly fluctuating signals in the DS and slower transients in the VS.
  • Correlated these dopamine dynamics with specific behavioral motifs like running, turning, and grooming on subsecond-to-minute timescales.
  • Found that cocaine disrupted action selection sequencing and DS-VS coordination.

Conclusions:

  • Distinct dopamine dynamics in the DS and VS jointly encode behavioral sequences during natural activity.
  • The DS signal appears to modulate the chaining of actions, while the VS signal is critical for action initiation and maintenance.
  • These findings elucidate the role of temporally differentiated striatal dopamine signaling in orchestrating complex behaviors.