Neurosciences
Program

Placek, K., Turek, K.C., Fullerton, J.N., and Brady, A.M. (2011, November). Relationships between behavioral abnormalities and set-shifting impairments in the neonatal ventral hippocampal lesion model of schizophrenia.

Poster presented at the Society for Neuroscience Annual Meeting, Washington, DC.

Abstract 

Rats with a neonatal ventral hippocampal lesion (NVHL), a developmental model of schizophrenia, exhibit behavioral abnormalities, such as disrupted prepulse inhibition (PPI), reduced social interaction, increased spontaneous locomotion, and potentiated locomotor response to stimulant drugs, that have been linked to clinical symptoms. NVHL rats also demonstrate executive function impairments on a T-maze strategy set-shifting task. In patients with schizophrenia, weak relationships exist between negative symptoms and executive function deficits, both of which are governed by the prefrontal cortex. Here, we examined performance in an operant-based set-shifting task, and explored potential correlations between set-shifting and behavioral abnormalities. Rats received bilateral hippocampal infusions of ibotenic acid (NVHL group) or artificial cerebrospinal fluid (sham group) on postnatal day 7. At adulthood, animals were tested on PPI, spontaneous locomotion, and social interaction with an unfamiliar partner. Rats were then trained on an operant set-shifting task where they were required to learn either a position-based or a visual cue-based rule on the first day of testing (Set), and then shift to the other rule on the second day of testing (Shift). Finally, animals were tested for amphetamine-induced (1.5 mg/kg, i.p.) locomotion. As previously observed in the T-maze task, NVHL rats were able to reach criterion performance on the first day’s rule (Set) as easily as shams, but took more trials to reach criterion and made more errors than shams on the second day’s rule (Shift). Unlike in the T-maze task, this deficit was dependent on the order of testing; the NVHL impairment was most clearly evident when rats shifted from a position-based rule to a visual cue-based rule. Set-shifting performance did not correlate with social interaction behavior, as might have been predicted from the clinical relationship between executive function and negative symptoms. However, unexpected correlations were found between set-shifting performance and rearing in the spontaneous locomotion task. In particular, the number of regressive errors was positively correlated with the number of rears. As regressive errors are governed by striatal areas, this correlation supports a dysfunction in corticostriatal circuits in the NVHL rat. Together, these results suggest that assessment of executive function deficits in the NVHL model may depend on the parameters of the particular set-shifting task, and that relationships between behavioral and cognitive abnormalities in NVHL animals are complex and do not necessarily follow patterns observed in patients with schizophrenia.