Dopamine Receptors Differentially Enhance Rule Coding in Primate Prefrontal Cortex Neurons

Abstract

Flexibly applying abstract rules is a hallmark feature of executive functioning represented by prefrontal cortex (PFC) neurons. Prefrontal networks are regulated by the neuromodulator dopamine, but how dopamine modulates high-level executive functions remains elusive. In monkeys performing a rule-based decision task, we report that both dopamine D1 and D2 receptors facilitated rule coding of PFC neurons, albeit by distinct physiological mechanisms. Dopamine D1 receptor stimulation suppressed neuronal firing while increasing responses to the preferred rule, thereby enhancing neuronal rule coding. D2 receptor stimulation, instead, excited neuronal firing while suppressing responses to the nonpreferred rule, thus also enhancing neuronal rule coding. These findings highlight complementary modulatory contributions of dopamine receptors to the neuronal circuitry mediating executive functioning and goal-directed behavior.

Examining the role of dopamine D2 and D3 receptors in Pavlovian conditioned approach behaviors

“…The mechanisms underlying the ability of dopamine in the core of the nucleus accumbens to evoke these responses have yet to be elucidated, but the D 2 -family of receptors may be involved. Likewise, local administration into other brain areas, such as prefrontal cortical regions might specifically affect goal-tracking behavior, as dopaminergic transmission in these regions is believed to be important in mediating goal-directed behaviors [42–45]. …”

Sensory and Working Memory Representations of Small and Large Numerosities in the Crow Endbrain

“…The numerosity code found in the crow endbrain is surprisingly reminiscent of findings for neurons in the monkey PFC and posterior parietal cortex (PPC) . In monkeys that discriminated visual numerosity in dot arrays (Eiselt and Nieder, 2013;Jacob and Nieder, 2014;Ott et al, 2014;Viswanathan and Nieder, 2015;Ott and Nieder, 2016;Ramirez-Cardenas et al, 2016;Nieder, 2016b), enumerated numerosity sequentially one by one in visual displays (Nieder et al, 2006), or performed hand movements (Sawamura et al, 2002(Sawamura et al, , 2010, tuned numerosity detectors were found. In the macaque PFC, neurons were also tuned supramodally to numerosity; that is, regardless of whether visual dots or acoustic sounds had to be assessed across time (Nieder, 2012).…”

“…fMRI adaptation indirectly revealed peaked tuning profiles in BOLD signals in the human IPS (Piazza et al, 2004) and PFC (Jacob and Nieder, 2009). Similar to our findings in crows and monkeys, these BOLD tuning curves also showed ratio-dependent tuning widths and are best described on a logarithmic number scale.…”

Neurophysiology of rule switching in the corticostriatal circuit

“…Recently, it has been shown using a task where primates either held or released a lever depending on whether a visual stimulus could be categorized as ‘greater than’ or ‘less than’ a sample stimulus of a quantity of dots that activation of different dopamine receptors in primate PFC can differentially modulate rule encoding, where D1 receptor activation increases signal to noise for neurons representing preferred rule activity, while D2 receptor activation decreases signal to noise for neurons representing a non-preferred or non-current rule(Ott et al, 2014). Taken together, this body of work has been able to identify neural correlates of rules in non-human primate PFC and has shown how these neural correlates pertain to a particular rule mostly when the rule represents a correct response option.…”

“…Further, identifying the respective roles of more precise cortical regions like the anterior cingulate cortex, prelimbic and infralimbic cortices will be important to identify what regions are responsible for what aspects of shifting rule-guided behavior. There exists some tantalizing evidence supporting a potential dissociable role for prelimbic and infralimbic cortices in mediating different aspects of flexible behavior(Rich and Shapiro, 2007, Oualian and Gisquet-Verrier, 2010), but in vivo neurophysiological experiments in conjunction with optogenetic approaches will provide more conclusive evidence. Dopamine in VS is known to be critical for flexible behavior(Haluk and Floresco, 2009).…”