Archival ReportInterneurons Are Necessary for Coordinated Activity During Reversal Learning in Orbitofrontal Cortex
Section snippets
Subjects
B6.129-Plaurtm1/Mlg/Plaurtm1/Mlg mice that have a null mutation in the gene that encodes the urokinase plasminogen activator receptor protein were genotyped as described previously (26). Behavioral and anatomical analyses were performed on adult (3- to 6-month-old) male littermates from at least six separate pedigrees bred on the C57BL/6J background for >20 generations. B6.129 male wild-type littermate mice were used as control animals. Experiments were conducted in accordance with University
Behavioral Impairment on First Reversal
Research in rats (32) and primates (33) has consistently shown behavioral impairment of OFC lesions on reversal learning. However, the effects of OFC lesions and other manipulations on reversal learning are typically transient (30, 34, 35), affecting only the first or early reversal problems in a set. Here, we show a similar deficit in mice performing a serial reversal task (Figure 1A–C). As in our previous reports (17, 28, 36), control and transgenic mice learned discriminations without
Discussion
We show that neurons in mouse OFC exhibit the same correlates as observed in rats and primates during reversal learning, encoding outcome expectations and associations formed to reward predictive cues (31, 37, 42, 43, 44). Mouse OFC neurons were responsive during decision and reward delivery epochs in discrimination and reversal phases. However, neural activity was only significantly correlated to behavioral performance during reversal. Our data also show that a neurodevelopmental example of an
Acknowledgments and Disclosures
Financial support for this study was provided by National Alliance for Research on Schizophrenia and Depression Young Investigator Award (EMP) and National Institute on Drug Abuse Grants DA108826 (Principal Investigator [PI]: EMP), DA015718 (PI: GS), and DA031695 (PI: MRR).
We thank D. Calu for neural recording assistance; S. Scahill for histology assistance; and G. Martins, S. Mullins, A. Gruber, A. Keller, P. O’Donnell, and J. Smith for insightful comments on the manuscript.
All authors
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