Homeostatic regulation of basal ganglia circuit for flexible behavior

Abstract

Behavioral inflexibility has been reported in various psychiatric disorders including drug addiction and schizophrenia. Considerable evidence has demonstrated a critical role for the basal ganglia in the flexibility of behavioral strategies. These processes are guided by the activity of two discrete neuron types, dopamine D1- or D2-receptor expressing medium spiny neurons (D1-/D2-MSNs) in the basal ganglia circuit. We used a reversible neurotransmission blocking technique to examine the role of D1- and D2-MSNs in the acquisition and reversal learning of a place discrimination task in the IntelliCage. We demonstrated that D1- and D2-MSNs do not mediate the acquisition of the task, but that suppression of activity in D2-MSNs impairs reversal learning and increased perseverative errors. Additionally, global knockout of the dopamine D2L receptor isoform produced a similar behavioral phenotype to D2-MSN-blocked mice. We also showed that D2L receptors are necessary for visual discrimination and reversal learning. These results suggest that D2L receptors and D2-MSNs have a critical role in the homeostatic regulation of basal ganglia circuit for flexible behaviors.