Research reportImpairments in set-shifting but not reversal learning in the neonatal ventral hippocampal lesion model of schizophrenia: Further evidence for medial prefrontal deficits

•Neonatal ventral hippocampal lesion (NVHL) developmentally models schizophrenia.•Operant set-shifting and reversal learning were examined in the NVHL rodent model.•NVHL animals were impaired on prefrontal-dependent set-shifting, but not reversal.•NVHL rats exhibited increased perseverative errors during set-shifting.•Cognitive deficits in NVHL rats are primarily driven by medial prefrontal cortex.

The executive function processes of set-shifting and reversal learning in rodents are mediated by the medial prefrontal cortex and the orbitofrontal cortex, respectively. Here, we investigated both set-shifting and reversal learning in a developmental animal model of schizophrenia, the neonatal ventral hippocampal lesion (NVHL) model. The NVHL manipulation is known to disrupt development of the medial prefrontal cortex, and to impair behaviors dependent on this area, but potential orbitofrontal abnormalities and reversal learning deficits are less well studied. Animals received excitotoxic lesions of the ventral hippocampus (NVHL) or a sham treatment during the first postnatal week, and all animals were subsequently tested in adulthood on either an operant set-shifting or an operant reversal task. Results indicated that NVHL animals were able to acquire a simple discrimination rule and exhibited normal reversal learning, but were impaired on a prefrontal-dependent set-shifting task. Furthermore, this set-shifting deficit was due to an increase in perseverative errors, which indicate difficulty suppressing a previously learned strategy and result from medial prefrontal insult. Together, these results confirm and extend the idea that cognitive impairments in the NVHL animal are primarily driven by medial prefrontal abnormalities, while the orbitofrontal cortex may remain relatively unaffected.