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Sökning: WFRF:(van den Munkhof M. H.)

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1.
  • Flores-Dourojeanni, J. P., et al. (författare)
  • Temporally Specific Roles of Ventral Tegmental Area Projections to the Nucleus Accumbens and Prefrontal Cortex in Attention and Impulse Control
  • 2021
  • Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 41:19, s. 4293-4304
  • Tidskriftsartikel (refereegranskat)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.
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2.
  • Flores-Dourojeanni, J. P., et al. (författare)
  • Inhibition of ventral tegmental area projections to the nucleus accumbens shell increases premature responding in the five-choice serial reaction time task in rats
  • 2023
  • Ingår i: Brain Structure & Function. - : Springer Science and Business Media LLC. - 1863-2653 .- 1863-2661.
  • Tidskriftsartikel (refereegranskat)abstract
    • Exaggerated impulsivity and attentional impairments are hallmarks of certain disorders of behavioural control such as attention-deficit/hyperactivity disorder (ADHD), schizophrenia and addiction. Pharmacological studies have implicated elevated dopamine (DA) levels in the nucleus accumbens shell (NAcbS) in impulsive actions. The NAcbS receives its DA input from the ventral tegmental area (VTA), and we have previously shown that optogenetic activation of VTA-NAcbS projections impaired impulse control and attention in the five-choice serial reaction time task (5-CSRTT) in rats. To better understand the role of VTA-NAcbS projections in impulsivity and attention, the present study sought to inhibit this projection using optogenetics. We demonstrate that inhibiting VTA-NAcbS efferents during the last seconds of the inter-trial interval (i.e. immediately before presentation of the instructive cue) induces exaggerated impulsive action, in the absence of changes in attentional or motivational parameters in the 5-CSRTT. Together with our earlier observations, this suggests that impulse control in the 5-CSRTT is tightly controlled by VTA-NAcbS activity, with deviations in both directions resulting in increased impulsivity.
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