Publication Type:Journal Article
Source:Neurobiol Learn Mem, Volume 90, Issue 2, p.339-46 (2008)
Keywords:Age Factors, Animals, Animals, Newborn, Association Learning, Attention, Brain Mapping, Choice Behavior, Cues, Dendritic Spines, Discrimination Learning, Dominance, Cerebral, Hippocampus, Ibotenic Acid, Male, Maze Learning, Memory, Short-Term, Microinjections, Motivation, Nerve Net, Orientation, Prefrontal Cortex, Problem Solving, Rats, Rats, Sprague-Dawley, Reversal Learning, Smell
Recent data showed that neonatal ventral hippocampus (VH) lesions, an approach used to model schizophrenia symptoms in rodents, produce premature deficits of working memory believed to be associated with early medial prefrontal cortex (mPFC) maldevelopment. This experiment expands the investigation of mPFC integrity in juvenile rats with neonatal VH lesions by assessing behavioral flexibility and dendritic spine density. Sixteen Sprague-Dawley male pups received bilateral microinjections of ibotenic acid in the VH or SHAM surgery on postnatal day (PND) 6. On PND 29 and 30, rats were subjected to a spatial shift task in a cross-maze; an attentional set-shifting task was then administered on two consecutive days, between PND 33 and PND 35. Rats were sacrificed at PND 36 and dendritic spine density in the mPFC was assessed using Golgi-Cox staining procedure. Results revealed impaired extra-dimensional shift in VH-lesioned rats and inconsistent reversal discrimination outcomes. Although lesioned animals displayed intact performance in the spatial shift, rates of perseverative responses were higher than normal in this task. Neonatal VH damage resulted in lower dendritic spine density in the mPFC than measured in control brains; however, no significant correlation was found between this outcome and behavioral data. Juvenile morphological and cognitive perturbations are consistent with the early emergence of mPFC anomalies following neonatal VH lesions. Results are discussed in relation with potential common mechanisms linking pre- and post-pubertal onsets of behavioral dysfunction.