title: NMDA lesions in the medial prefrontal cortex impair the ability to inhibit responses during reversal of a simple spatial discrimination.
abstract: Although lesion studies suggest that the rat medial prefrontal cortex (mPFc) is involved in the process necessary for reversal of a particular set of contingencies, the nature of lesion-induced deficits is unclear. The involvement of rat mPFc in reversal of a simple spatial discrimination was examined in the present study. Our hypothesis was that lesion-induced deficits may reflect a failure to inhibit a learned instrumental response. Lister Hooded rats were trained on a spatial discrimination task (SD), which required a correct barpress matching the cue location, then they were trained on reversal of SD (SDR), which required a correct barpress opposite to the cue location. Rats with mPFc lesions showed a slower learning rate compared to the controls. However, behavior of the lesioned rats during early and later reversal differed. During the initial SDR, the lesioned rats showed a greater number of barpresses during the intertrial interval and a slightly higher percent correct responses than that of the controls. Our data suggest that damage to mPFc may produce a lack of response inhibition, leading to an increase in nondiscriminated bapresses, thereby yielding a 'facilitation' during early reversal. mPFc lesion did not affect either open field activity or prepulse inhibition (PPI), a frequently used measure of sensorimotor gating. Disruption of reversal learning following damage to mPFc is partly due to a failure to inhibit instrumental responses, rather than to disruption of other processes involved in sensorimotor gating or general activity.
authors.affiliation: Institute of Neuroinformatics, University Zuerich, Winterthurerstrasse 190 Zuerich, Switzerland.
authors.forename: Rodrigo F
authors.initials: RF
authors.lastname: Salazar
authors.forename: Wesley
authors.initials: W
authors.lastname: White
authors.forename: Laurent
authors.initials: L
authors.lastname: Lacroix
authors.forename: Joram
authors.initials: J
authors.lastname: Feldon
authors.forename: Ilsun M
authors.initials: IM
authors.lastname: White
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001927:Brain Diseases / Q000139:chemically induced / Q000503:physiopathology; D004193:Discrimination Learning / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity*; D009433:Neural Inhibition / Q000502:physiology*; D017397:Prefrontal Cortex / Q000293:injuries* / Q000502:physiology; D051381:Rats; D012193:Reversal Learning / Q000502:physiology; D013028:Space Perception / Q000502:physiology*; D013997:Time Factors
chemical_list: D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate