An opioid-gated thalamoaccumbal circuit for the suppression of reward seeking in mice

Kelsey M. Vollmer, Lisa M. Green, Roger I. Grant, Kion T. Winston, Elizabeth M. Doncheck, Christopher W. Bowen, Jacqueline E. Paniccia, Rachel E. Clarke, Annika Tiller, Preston N. Siegler, Bogdan Bordieanu, Benjamin M. Siemsen, Adam R. Denton, Annaka M. Westphal, Thomas C. Jhou, Jennifer A. Rinker, Jacqueline F. McGinty, Michael D. Scofield and James M. Otis ()
Additional contact information
Kelsey M. Vollmer: Medical University of South Carolina
Lisa M. Green: Medical University of South Carolina
Roger I. Grant: Medical University of South Carolina
Kion T. Winston: Medical University of South Carolina
Elizabeth M. Doncheck: Medical University of South Carolina
Christopher W. Bowen: Medical University of South Carolina
Jacqueline E. Paniccia: Medical University of South Carolina
Rachel E. Clarke: Medical University of South Carolina
Annika Tiller: Medical University of South Carolina
Preston N. Siegler: Medical University of South Carolina
Bogdan Bordieanu: Medical University of South Carolina
Benjamin M. Siemsen: Medical University of South Carolina
Adam R. Denton: Medical University of South Carolina
Annaka M. Westphal: Medical University of South Carolina
Thomas C. Jhou: Medical University of South Carolina
Jennifer A. Rinker: Medical University of South Carolina
Jacqueline F. McGinty: Medical University of South Carolina
Michael D. Scofield: Medical University of South Carolina
James M. Otis: Medical University of South Carolina

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Suppression of dangerous or inappropriate reward-motivated behaviors is critical for survival, whereas therapeutic or recreational opioid use can unleash detrimental behavioral actions and addiction. Nevertheless, the neuronal systems that suppress maladaptive motivated behaviors remain unclear, and whether opioids disengage those systems is unknown. In a mouse model using two-photon calcium imaging in vivo, we identify paraventricular thalamostriatal neuronal ensembles that are inhibited upon sucrose self-administration and seeking, yet these neurons are tonically active when behavior is suppressed by a fear-provoking predator odor, a pharmacological stressor, or inhibitory learning. Electrophysiological, optogenetic, and chemogenetic experiments reveal that thalamostriatal neurons innervate accumbal parvalbumin interneurons through synapses enriched with calcium permeable AMPA receptors, and activity within this circuit is necessary and sufficient for the suppression of sucrose seeking regardless of the behavioral suppressor administered. Furthermore, systemic or intra-accumbal opioid injections rapidly dysregulate thalamostriatal ensemble dynamics, weaken thalamostriatal synaptic innervation of downstream neurons, and unleash reward-seeking behaviors in a manner that is reversed by genetic deletion of thalamic µ-opioid receptors. Overall, our findings reveal a thalamostriatal to parvalbumin interneuron circuit that is both required for the suppression of reward seeking and rapidly disengaged by opioids.

Date: 2022
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DOI: 10.1038/s41467-022-34517-w

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