The role of prefrontal dopamine D1 receptors in the neural mechanisms of associative learning.
Dopamine is thought to play a major role in learning. However, while dopamine D1 receptors (D1Rs) in the prefrontal cortex (PFC) have been shown to modulate working memory-related neural activity, their role in the cellular basis of learning is unknown. We recorded activity from multiple electrodes while injecting the D1R antagonist SCH23390 in the lateral PFC as monkeys learned visuomotor associations. Blocking D1Rs impaired learning of novel associations and decreased cognitive flexibility but spared performance of already familiar associations. This suggests a greater role for prefrontal D1Rs in learning new, rather than performing familiar, associations. There was a corresponding greater decrease in neural selectivity and increase in alpha and beta oscillations in local field potentials for novel than for familiar associations. Our results suggest that weak stimulation of D1Rs observed in aging and psychiatric disorders may impair learning and PFC function by reducing neural selectivity and exacerbating neural oscillations associated with inattention and cognitive deficits.
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
M Victoria
MV
Puig
Earl K
EK
Miller
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001552:Benzazepines / Q000494:pharmacology; D001931:Brain Mapping; D018492:Dopamine Antagonists / Q000494:pharmacology; D008253:Macaca mulatta; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010775:Photic Stimulation; D017397:Prefrontal Cortex / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D012372:ROC Curve; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D013057:Spectrum Analysis; D013997:Time Factors
D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390