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

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.

Operant conditioning deficits and modified local field potential activities in parvalbumin-deficient mice

“…This significant set of changes is likely to be related with the increase contribution of food reward across training, a typical characteristic of NAc neurons 51 and with some but not all neurophysiological deficits seen in GABAergic interneurons of PV-deficient mice 52 . During social interaction in normal conditions, the increase of the neurotransmitter DA in the NAc would excite the PV-expressing fast-spiking interneurons (PV-FSI) directly through D1-type receptors or indirectly through D2-type receptors 53 , and cortical projections from mPFC to NAc would contribute to maintaining the E/I balance and regulating reward-seeking processes 28 . This would increase the inhibitory activity of the PV-FSI on the medium spiny neurons (MSN), which would generate oscillations in -frequency range.…”

The Role of Parvalbumin Interneurons in Neurotransmitter Balance and Neurological Disease

“…Ethanol consumption however, decreases Pv-FSI activity, and facilitates activation of D1-like and D2-like receptors on the cell surfaces of these interneurons (42), and increases dopamine release in the NAc. Interestingly however, some also report no significant changes in dopamine release directly related to Pv-FSI activation (43). Other studies also have shown a strong influence of dopamine upon cortical Pv-FSIs.…”

“…Although, glutamate dysregulation is a possible explanation for cognitive dysfunction and consequent compulsive rewardseeking during substance abuse, there is more to the story of this molecular mechanism since the contribution of interneurons in glutamate circuitries have not been fully established. Pv-FSI, specifically, have been implicated in studies on cognition and reward-seeking (5,43). Even though Pv-FSI constitute as little as only 2% of the neuronal population in the mPFC and NAc, they are adept in controlling the glutamatergic outputs of pyramidal neurons in the mPFC (13), while also modulating GABAergic MSNs in the striatum (35,37).…”

“…Recent developments in the field of reward and drug addiction have been to elucidate the role of interneurons and their involvement in brain circuitry associated with impaired cognition and behavior in drug abuse. Moreover, studies modulated Pv-FSI activity to see how it alters reward-seeking behaviors for natural rewards like sucrose and drugs of abuse like ethanol (43,72) amphetamine (37), and cocaine (39,73). Operant conditioning paradigms have served as an important tool to assess and understand reward behavior.…”

“…In fact, activation of Pv-FSI in the mPFC and NAc both result in behavioral changes to reward (37). Research has focuses on Pv-FSI in the cortex (43), and some on the striatum (72) and their role in reward-seeking. One study has found that Pv-FSI in the striatum are involved in reward-conditioned behavioral performance in an experience-dependent manner in which more learning occurs.…”