Abstract
The posterior subdivision of the medial orbitofrontal cortex (mOFC-p) mediates the willingness to expend effort to reach a selected goal. However, the neural circuitry through which the mOFC-p modulates effort-related function is as yet unknown. The mOFC-p projects prominently to the posterior ventral tegmental area (pVTA). Therefore, we analyzed the role of the mOFC-p and interactions with the pVTA in effort-related responding using a combination of behavioral, pharmacological, and neural circuit analysis methods in rats. Pharmacological inhibition of the mOFC-p was found to increase lever pressing for food under a progressive ratio (PR) schedule of reinforcement. These findings provide further support for a modulation of effort-related function by the mOFC-p. Then, we investigated effects of disconnecting the mOFC-p and pVTA on PR responding using unilateral pharmacological inhibition of both areas. This asymmetric intervention was also found to increase PR responding suggesting that the mOFC-p controls effort-related function through interactions with the pVTA. Possibly, a reduced excitatory mOFC-p drive on pVTA gamma-aminobutyric acid (GABA)ergic relays disinhibits VTA dopamine neurons which are known to support PR responding. Collectively, our findings suggest that the mOFC-p and pVTA are key components of a neural circuit mediating the willingness to expend effort to reach a goal.
Highlights
The orbitofrontal cortex (OFC) is an anatomically and functionally heterogeneous region that supports learning and decisionmaking in multiple ways, for instance, by providing predictions about outcomes associated with actions (Rudebeck and Murray 2014; Wilson et al 2014)
An exploratory study in a small number of rats indicated that optogenetical stimulation of the mOFC-p had opposite effects and reduced progressive ratio (PR) responding
We show that the mOFC-p controls effort-related responding through interactions with posterior ventral tegmental area (pVTA) GABAergic mechanisms
Summary
The orbitofrontal cortex (OFC) is an anatomically and functionally heterogeneous region that supports learning and decisionmaking in multiple ways, for instance, by providing predictions about outcomes associated with actions (Rudebeck and Murray 2014; Wilson et al 2014). Given that the output of the OFC is excitatory (Geisler et al 2007), OFC stimulation was supposed to reduce VTA dopamine neuron activity via inhibitory relays such as VTA gamma-aminobutyric acid (GABA) ergic interneurons (Takahashi et al 2011). In line with this account, microinjection of GABAA/B receptor agonists into the pVTA induced stimulant behavioral effects and, for instance, enhanced motor activity (Arnt and Scheel-Krueger 1979; Wirtshafter and Klitenick 1989; Boehm 2nd et al 2002). We hypothesized that the mOFC-p governs effort-related responding via GABAergic mechanisms in the pVTA
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