Regulation of Pv‐specific interneurons in the medial prefrontal cortex and reward‐seeking behaviors
Lailun Nahar, Caleb A. Grant, Cameron Hewett, Diego Cortés, Ashlie N. Reker, Seungwoo Kang, Doo‐Sup Choi, Hyung Wook Nam
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.