Ventral striatal processing of prefrontal inputs and phasic dopamine during rule switching

• Applicant: Dr. Florian Bähner
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 265323688

In novel situations individuals often learn through feedback which cues predict reward. Information about actions and their consequences needs to be updated whenever rules switch. Rule switching and the involved brain circuits are conserved across mammals. These brain circuits contain the nucleus accumbens (NAc) of the ventral striatum and the medial prefrontal cortex (mPFC). Dopamine (DA) transients both predict rewards and suppress interactions of mPFC and NAc. We will focus on the NAc that has been proposed to serve as a central gateway where converging inputs help to optimize reward outcome. Yet, the neuronal mechanisms of rule switching are largely unknown. To study the neural correlates of rule switching in freely moving rats, we propose to perform tetrode recordings and fast scan cyclic voltammetry in NAc and mPFC during performance of an operant version of a strategy set shifting paradigm. Experiments will be guided by two hypotheses. First, mPFC representations of a novel rule are integrated in the NAc to optimize reward outcome. We predict that mPFC-NAc interactions transiently increase after the rule switch when the animal has not yet learned the novel rule. To determine interactions of mPFC and NAc, coordinated firing of neuronal assemblies and their temporal organization by oscillations will be examined. Second, cues that predict reward elicit DA transients. We hypothesize that after the rule has switched, the old cue does not predict reward anymore and therefore stops eliciting DA transients. Artificially maintaining the DA signal concurrent with the old cue will thus prevent behavioral rule switches. These artificial DA transients are also predicted to suppress mPFC-NAc interactions. Towards these aims, we will initially examine the relation of the phasic DA transients in the NAc to behavioral performance and neuronal activity in the NAc during rule switching. In a second set of experiments, after the rule switch, the DA transient will be artificially restored concurrent with the now unrewarded cue using optogenetic stimulation of DAergic neurons. During this manipulation we will track behavioral performance and mPFC-NAc interactions. Together, our project shall help to understand the role of DA transients in rule switches and associated NAc representations. These findings have implications for cognitive flexibility that is impaired in major neuropsychiatric disorders.

• DFG Programme: Research Grants