PreprintCited by 3Neuropeptides and Animal PhysiologyNeurotransmitter Receptor Influence on BehaviorNeuroendocrine regulation and behavior

Endogenous opioid dynamics in the dorsal striatum sculpt neural activity to control goal-directed action

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Gowrishankar, Raajaram, Hjort, Madelyn, Elerding, Abigail J, Shirley, Sofia E, Van Tilburg, Josie, Marcus, David J, Senthilkumar, Pranav, Abrera, Khalid A +9 more·2024·bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Endogenous neuropeptides are uniquely poised to regulate neuronal activity and behavior across multiple timescales. Traditional studies ascribing neuropeptide contributions to behavior lack spatiotemporal precision. The endogenous opioid dynorphin is highly enriched in the dorsal striatum, known to be critical for regulating goal-directed behavior. However, the locus, the precise timescale, or functional role of endogenous dyn-KOR signaling on goal-directed behavior is unknown. Here, we report that local, time-locked dynorphin release from the dorsomedial striatum is necessary and sufficient for goal-directed behavior using a suite of high resolution modern approaches including in vivo two-photon imaging, neuropeptide biosensor detection, conditional deletions and time-locked optogenetic manipulations. We discovered that glutamatergic axon terminals from the basolateral amygdala evoke striatal dynorphin release, resulting in retrograde presynaptic GPCR inhibition during behavior. Collectively, our findings isolate a causal role for endogenous neuropeptide release at rapid timescales, and subsequent GPCR activity for tuning and promoting fundamental goal-directed behaviors.

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Crossref · 10.1101/2024.05.20.595035

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Authors
Gowrishankar, R., Hjort, M., Elerding, A. J., Shirley, S. E., Van Tilburg, J., Marcus, D. J., Senthilkumar, P., Abrera, K. A., Sumarli, D., Motovilov, K., Lau, V., Gordon-Fennell, A. A., Zhou, Z. C., Dong, C., Tian, L., Stuber, G. D., & Bruchas, M. R.
Affiliations
  • University of Washington (US)
  • University of California, Davis (US)
  • Max Planck Florida Institute for Neuroscience (US)
Corresponding author
Bruchas, Michael R.
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2024-05-20
OpenAlex
W4398175943
Cited by
3
References
91
Citations by year
2025: 1 · 2024: 1 · 2023: 1
Type
posted content
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • SSRN Electronic Journal (acceptedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords
dorsal striatum, goal-directed behavior, kappa opioid receptor, neuropeptide release, basolateral amygdala, glutamatergic synapses, presynaptic inhibition

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