Characterization and mu opioid receptor sensitivity of neuropeptide Y interneurons in the mouse nucleus accumbens

Cassandra L Retzlaff, Patrick E. Rothwell

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Inhibitory interneurons represent less than 5% of neurons within the nucleus accumbens, but are critical for proper microcircuit function within this brain region. In the dorsal striatum, neuropeptide Y is expressed by two interneuron subtypes (low-threshold spiking interneurons and neurogliaform interneurons) that exhibit mu opioid receptor sensitivity in other brain regions. However, few studies have assessed the molecular and physiological properties of neuropeptide Y interneurons within the nucleus accumbens. We used a transgenic reporter mouse to identify and characterize neuropeptide Y interneurons in acute nucleus accumbens brain slices. Nearly all cells exhibited electrophysiological properties of low-threshold spiking interneurons, with almost no neurogliaform interneurons observed among neuropeptide Y interneurons. We corroborated this pattern using fluorescent in situ hybridization, and also identified a high level of mu opioid receptor expression by low-threshold spiking interneurons, which led us to examine the functional consequences of mu opioid receptor activation in these cells using electrophysiology. Mu opioid receptor activation caused a reduction in the rate of spontaneous action potentials in low-threshold spiking interneurons, as well as a decrease in optogenetically-evoked GABA release onto medium spiny neurons. The latter effect was more robust in female versus male mice, and when the postsynaptic medium spiny neuron expressed the Drd1 dopamine receptor. This work is the first to examine the physiological properties of neuropeptide Y interneurons in the nucleus accumbens, and show they may be an important target for mu opioid receptor modulation by endogenous and exogenous opioids.

Original languageEnglish (US)
Article number109212
StatePublished - Nov 1 2022

Bibliographical note

Funding Information:
Research reported in this publication was supported by the University of Minnesota's MnDRIVE (Minnesota's Discovery, Research and Innovation Economy) initiative; the Center for Neural Circuits in Addiction and NIDA Core Center Grant P30DA048742 ; and National Institutes of Health grants DA037279 and DA048946 (PER). The viral vectors used in this study were generated by the University of Minnesota Viral Vector and Cloning Core. We thank Drs. Esther Krook-Magnuson, Emilia Lefevre, and Brian Trieu for helpful discussions.

Publisher Copyright:
© 2022 Elsevier Ltd


  • Electrophysiology
  • Fluorescent in situ hybridization
  • Interneuron
  • Mu opioid receptor
  • Nucleus accumbens
  • Optogenetics

PubMed: MeSH publication types

  • Journal Article


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