Nucleus accumbens dopamine D2-receptor expressing neurons control behavioral flexibility in a place discrimination task in the IntelliCage.
Considerable evidence has demonstrated a critical role for the nucleus accumbens (NAc) in the acquisition and 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). Here we used the IntelliCage, an automated group-housing experimental cage apparatus, in combination with a reversible neurotransmission blocking technique to examine the role of NAc D1- and D2-MSNs in the acquisition and reversal learning of a place discrimination task. We demonstrated that NAc 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. These results suggest that D2L receptors and NAc D2-MSNs act to suppress the influence of previously correct behavioral strategies allowing transfer of behavioral control to new strategies.
Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Tom
T
Macpherson
Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Makiko
M
Morita
Department of Pharmacology, Beckman Institute, University of Illinois, Urbana, Illinois 61801, USA.
Yanyan
Y
Wang
Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
Toshikuni
T
Sasaoka
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Akira
A
Sawa
Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan hikida@tk.med.kyoto-u.ac.jp.
Takatoshi
T
Hikida
D000818:Animals; D004192:Discrimination, Psychological / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D009714:Nucleus Accumbens / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000502:physiology*; D012193:Reversal Learning / Q000502:physiology*
D020033:Protein Isoforms; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C113776:dopamine D2L receptor