Regulation of Pv-specific interneurons in the medial prefrontal cortex and reward-seeking behaviors

Lailun Nahar, Caleb A. Grant, Cameron Hewett, Diego Cortes, Ashlie N. Reker, Seungwoo Kang, Doo Sup Choi, Hyung W. Nam

Research output: Contribution to journalArticle

Abstract

The corticostriatal circuitry and its glutamate-γ-aminobuturic acid (GABA) interactions play an essential role in regulating neuronal excitability during reward-seeking behavior. However, the contribution of GABAergic interneurons in the corticostriatal circuitry remains unclear. To investigate the role of GABAergic interneurons, we focused on parvalbumin-expressing fast-spiking interneurons (Pv-FSI) in the corticostriatal circuitry using the designer receptors exclusively activated by designer drugs approach in a Pv-Cre mouse model. We hypothesize that Pv-FSI activation elicits changes in cortical glutamate levels and reward-seeking behaviors. To determine molecular and behavioral effects of Pv-FSI, we performed microdialysis and operant conditioning tasks for sucrose and alcohol rewards. In addition, we also examined how alcohol reward itself affects Pv-FSI functioning. Interestingly, our microdialysis results demonstrate that alcohol exposure inhibits Pv-FSI functioning in the medial prefrontal cortex (mPFC) and this consequently can regulate glutamate levels downstream in the nucleus accumbens. For sucrose reward-seeking behaviors, Pv-FSI activation in the mPFC increases sucrose self-administration whereas it does not promote alcohol seeking. For alcohol rewards, however, Pv-FSI activation in the mPFC results in increased compulsive head entry in operant chambers during devaluation procedures. Overall, our results suggest that not only do Pv-FSI contribute to changes in the cortical microcircuit and reward-seeking behaviors but also that alcohol affects Pv-FSI neurotransmission. Therefore, Pv-FSI has prompted interest in their role in maintaining a balance in neuronal excitation/inhibition and in regulating reward-seeking processes such as compulsivity, all of which are important factors for excessive alcohol seeking. (Figure presented.).

Original languageEnglish (US)
JournalJournal of neurochemistry
DOIs
StateAccepted/In press - 2020

Keywords

  • glutamate
  • microdialysis
  • mPFC
  • parvalbumin expressing fast-spiking interneurons (Pv-FSI)
  • reward-seeking

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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