Dopaminergic Modulation of Executive Control Signals in Primate Prefrontal Cortex Neurons

Abstract

Executive control refers to the ability of animals and humans to select appropriate actions for achieving goals under varying environmental conditions. Working memory, for example, enables us to manipulate and integrate information about the sensory environment without needing constant sensory input. This information can then be integrated with internal representations about rules, plans, or goal values to guide behavior. Executive functions rely on the integrity of prefrontal cortex (PFC), where single neurons signal information relevant for guiding behavior. PFC networks are strongly innervated by midbrain dopmine neurons, which regulate a variety of executive control functions. However, the neuronal basis for dopaminergic control of executive functions is largely unknown.

In this thesis, we performed several studies addressing dopamine modulation of neuronal signals relevant for executive control. We trained macaque monkeys to perform several tasks requiring a range of executive control functions and recorded single neurons in PFC while stimulating or blocking specific dopamine receptors at the vicinity of the recorded neurons using micro-iontophoresis. We investigated how dopamine influences neuronal signals carrying behavioral relevant information at single neuron and population levels and addressed possible mechanisms of action using computational models of prefrontal networks.

We show that dopamine and dopamine receptors modulate a variety of signals relevant for executive control. Fist, dopamine enhanced visual signals in PFC relevant for perceptual decisions. Next, working memory activity during subsequent delay periods was strongly improved by activating D2 family receptors, which also controlled dynamic properties of PFC networks. Stimulating either D1 or D2 family receptors enhanced signals about behavioral rules by distinct physiological mechanisms. On the other hand, D1 and D2 family receptors oppositely modulated representation of goal values. Computational modeling proposed a specific mechanism by which dopamine receptors change synaptic properties, suggesting that dopamine acts primarily by changing interneuron-to-pyramidal signaling.

These results show that dopamine receptors assume complementary as well as opposite roles in modulating executive control. Dopamine receptors cooperatively regulate working memory and behavioral flexibility while oppositely influencing reward signals. Thus, dopamine functions might dissociate between different executive control functions. Together, our results suggest that dopamine gates sensory input to PFC and subsequently stabilizes prefrontal representations relevant for executive control. Thus, dopamine modulates the flow of information through PFC, controlling the selection of appropriate actions during goal-directed behavior.