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.

Concurrent measures of impulsive action and choice are partially related and differentially modulated by dopamine D1- and D2-like receptors in a rat model of impulsivity

“…The nucleus accumbens (NAc) controls different facets of impulsivity (Basar et al, 2010) but its core and shell sub-regions have been proposed to have distinct roles in modulating impulsive behaviors. Thus, optogenetic stimulation of the ventral striatum (VTA)-NAc shell pathway increased impulsive action (Flores-Dourojeanni et al, 2021), while stimulation of VTA-NAc core pathway decreased delay-related impulsive choice (Saddoris et al, 2015). An involvement of the NAc in risky decision-making is also supported by ex- and in-vivo DA receptor expression in NAc shell but not core (Freels et al, 2020; Simon et al, 2011).…”

A Role for Serotonin in Modulating Opposing Drive and Brake Circuits of Impulsivity

“…In particular, the NAc and its core and shell subregions have been extensively studied for their individual roles in impulsive action through reaction time tests, with pharmacological manipulations and deep brain stimulation of the shell subregion causing elevated premature responding (Sesia et al, 2010;Feja et al, 2014). Optogenetic stimulation of projections from the VTA to the NAc shell also increased premature responding during a long inter-trial interval in the 5CSRTT (Flores-Dourojeanni et al, 2021). Additionally, prefrontal cortical regions modulate impulsive action, though they are more often associated with assigning value to different decisions and choosing between actions (OFC, mPFC).…”

Ascorbic acid derived carbon dots promote circadian rhythm and contribute to attention deficit hyperactivity disorder

“…Attention–Deficit/hyperactivity Disorder (ADHD) is one of the most prevalent and highly heritable psychiatric disorders in childhood 1 2 , affecting about 5-7% of the population 3 , and the number has been continuously increasing these years. ADHD is characterized by hyperactivity, impulsivity and inattention 4 , which impairs normal development of social and academic functions in children, and usually leads to secondary problems, such as drug addiction in adults 5 .…”