Temporally Specific Roles of Ventral Tegmental Area Projections to the Nucleus Accumbens and Prefrontal Cortex in Attention and Impulse Control

Abstract

Deficits in impulse control and attention are prominent in the symptomatology of mental disorders such as attention deficit hyperactivity disorder (ADHD), substance addiction, schizophrenia, and bipolar disorder, yet the underlying mechanisms are incompletely understood. Frontostriatal structures, such as the nucleus accumbens (NAcb), the medial prefrontal cortex (mPFC), and their dopaminergic innervation from the ventral tegmental area (VTA) have been implicated in impulse control and attention. What remains unclear is how the temporal pattern of activity of these VTA projections contributes to these processes. Here, we optogenetically stimulated VTA dopamine (DA) cells, as well as VTA projections to the NAcb core (NAcbC), NAcb shell (NAcbS), and the mPFC in male rats performing the 5-choice serial reaction time task (5-CSRTT). Our data show that stimulation of VTA DA neurons, and VTA projections to the NAcbC and the mPFC immediately before presentation of the stimulus cue, impaired attention but spared impulse control. Importantly, in addition to reducing attention, activation of VTA-NAcbS also increased impulsivity when tested under a longer intertrial interval (ITI), to provoke impulsive behavior. Optogenetic stimulation at the beginning of the ITI only partially replicated these effects. In sum, our data show how attention and impulsivity are modulated by neuronal activity in distinct ascending output pathways from the VTA in a temporally specific manner. These findings increase our understanding of the intricate mechanisms by which mesocorticolimbic circuits contribute to cognition. SIGNIFICANCE STATEMENT Deficits in impulse control and attention are prominent in the symptomatology of several mental disorders, yet the brain mechanisms involved are incompletely understood. Since frontostriatal circuits have been implicated in impulse control and attention, we here examined the role of ascending projections from the midbrain ventral tegmental area (VTA) to the nucleus accumbens (NAcb) and prefrontal cortex (PFC). Using optogenetics to individually stimulate these projections with time-locked precision, we distinguished the role that each of these projections plays, in both impulse control and attention. As such, our study enhances our understanding of the neuronal circuitry that drives impulsive and attentive behavior.