Feature Review
Dopamine and Cognitive Control in Prefrontal Cortex

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Highlights

Dopamine enables successful cognitive control in prefrontal cortex.

Dopamine receptors in prefrontal cortex control three key aspects of cognitive control – gating, maintaining, and relaying.

The two major dopamine receptor families, D1R and D2R, assume complementary roles in cognitive control.

Dopamine receptors are differentially integrated in cortical circuit components subserving distinct aspects of cognitive control.

Cognitive control, the ability to orchestrate behavior in accord with our goals, depends on the prefrontal cortex. These cognitive functions are heavily influenced by the neuromodulator dopamine. We review here recent insights exploring the influence of dopamine on neuronal response properties in prefrontal cortex (PFC) during ongoing behaviors in primates. This review suggests three major computational roles of dopamine in cognitive control: (i) gating sensory input, (ii) maintaining and manipulating working memory contents, and (iii) relaying motor commands. For each of these roles, we propose a neuronal microcircuit based on known mechanisms of action of dopamine in PFC, which are corroborated by computational network models. This conceptual approach accounts for the various roles of dopamine in prefrontal executive functioning.

Section snippets

Prefrontal Cortex, the Central Executive of the Brain

Humans and other animals can engage in flexible behaviors beyond simple stimulus–response associations. The ability to flexibly adjust behavioral responses to produce goal-directed and intelligent behaviors is commonly referred to as ‘cognitive control’ or executive control functions (see Glossary). The PFC at the anterior pole of the endbrain is crucially involved in functions that enable cognitive control, such as stimulus selection, working memory, rule switching, decision making, and others

Dopamine in the PFC

Processing in the PFC, however, is by no means self-contained. If and how information is passed on from one functional group of PFC neurons to the next is under the crucial influence of the neuromodulatory messenger substance dopamine. The neuromodulator dopamine is synthesized by dedicated neurons in the midbrain that send their axons to many brain regions including the PFC 10, 11. When these neurons fire, dopamine is broadly released (from varicosities and terminal endings) into the neural

Dopamine Transients Show Characteristics of a Gating Signal

The first component of successful cognitive control is representing relevant sensory stimuli from the environment (Figure 3A). PFC neurons represent basic sensory signals and are tuned, for instance, to motion direction, motion speed, and the luminance of visual stimuli 58, 59, 60. In contrast to neurons in early sensory areas that encode veridical information of the physical stimulus features, the behavioral relevance of stimuli is reflected in PFC neuronal responses 58, 61, 62, 63. For

Dopamine Modulation of Information Maintenance in Working Memory

After relevant sensory signals have passed the initial input gate, they need to be maintained ‘online’ in brain networks (Figure 3A). As a fundamental ability for any complex behavior, the concept of working memory encompasses the capacity to retain immediately past information, to process this information contextually, and to use it to guide goal-directed behavior. A wealth of behavioral studies have established that prefrontal dopamine alters working-memory performance in humans and animals

D2Rs Modulate Motor Signals

Once the incoming sensory information has been evaluated according to the rule of the game, an appropriate motor plan must be generated and executed. In the telephone example used in the introduction, this amounts to actually picking up the telephone if it is ringing at our home. Dopamine has been found to also influence this third function in the temporal sequence of a cognitive delay task – the relaying of motor commands to motor structures.

In PFC, microinfusion of D1R antagonists or D2R

Concluding Remarks

We have outlined how prefrontal dopamine enables successful cognitive control in three domains. First, dopamine gates sensory input via fast modulation of excitatory glutamatergic afferents. Second, dopamine allows updating of prefrontal representations as well as subsequent stabilization through complementary dopamine receptor mechanisms. Finally, dopamine controls the flow of information to downstream target areas preparing motor commands. This account has various implications for future

Acknowledgments

We thank Naoshige Uchida and Pooja Viswanathan for comments on this manuscript. This research was supported by DFG grants NI 618/5-1 and NI 618/5-2 to Andreas Nieder.

Glossary

Dopamine
a neurotransmitter released by the midbrain dopamine system, a small set of midbrain nuclei exerting widespread neuromodulatory control over brain function.
Executive control functions
a set of cognitive functions enabling goal-directed execution of behavior, such as working memory, allocation of attention, rule following, categorization, and others.
Gain computation
changing the sensitivity of a neuron by a multiplicative factor in the firing rate following an input.
Inhibitory interneuron
a

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