Behavioural Brain Research 146 (2003) 57–63 Research report Recovery from infant medial frontal cortical lesions in rats is reversed by cortical lesions in adulthood Agnes Dallison, Bryan Kolb ∗ Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, Canada T1K 3M4 Abstract Previous studies have shown that when the medial prefrontal cortex (mPFC) is removed at 7–10 days of age there is a spontaneous filling of the lesion cavity and a nearly complete restitution of behaviour. In the current study animals received mPFC lesions on postnatal day 10 and on day 160 the tissue occupying the mPFC region was again removed. Behavioural performance on the Morris water task was compared to animals with either only day 10 mPFC lesions or only day 160 mPFC lesions. Rats with the combined day 10 and day 160 lesions or day 160 lesions were severely impaired at the task whereas the rats with only day 10 lesions showed complete recovery. An analysis of dendritic arborization in pyramidal neurons adjacent to the lesion showed increased dendritic arborization in the basilar fields in both the P10 groups but this was not associated with functional recovery in the animals with the two mPFC lesions. It thus appears that the tissue that filled in the mPFC lesions on day 10 was functional. © 2003 Elsevier B.V. All rights reserved. Keywords: Recovery of function; Prefrontal cortex; Dendritic arborization 1. Introduction Damage to the medial prefrontal cortex (mPFC) of the neonatal rat at 7–10 postnatal days old (P7–P10) is associated with a far better functional outcome in adult- hood than similar damage either earlier or later in life [1–6,8–19,21,22]. This functional recovery is correlated with a variety of morphological changes including anoma- lous thalamocortical projections [5,13], an absence of thalamic degeneration in the dorsomedial nucleus [14,22], increased dopaminergic terminals in adjacent cortex [2,13] increased arborization and increased spine density in the remaining cortex [10,13] and the regrowth of at least some of the lost tissue [12,15] These anatomical findings are presumed to be related to the functional outcome but by themselves, they simply provide interesting correlations. The real test is to block or reverse the anatomical changes and then measure the functional effects. The goal of the current study was to reverse the functional recovery seen after neonatal mPFC lesions by removing the regrown mPFC tissue in adulthood. Our hypothesis was that if the new midline frontal tissue was functional, then removal of this tissue ought to reverse the behavioural outcome. We believed that the tissue should be at least partially functional ∗ Corresponding author. Tel.: +1-403-329-2405; fax: +1-403-329-2775. E-mail address: Kolb@uleth.ca (B. Kolb). because it had not only regrown about 60% of the volume of the lost tissue but it had also regrown some of the normal connections of the lost tissue [12]. On the other hand, be- cause there are many other morphological correlates of the functional recovery it was possible that the regrown mPFC tissue was not necessary for the observed functional recov- ery. Rats were given mPFC on postnatal day 10, raised to adulthood, and a subgroup of the animals then had the tis- sue that had filled in the lesion cavity removed again. Per- formance of the infant-operated groups on the Morris water task was compared to sham control animals and animals that only had frontal lesions in adulthood. The brains were later processed for Golgi–Cox staining and dendritic arborization was quantified for the layer III pyramidal cells in the cortex adjacent to the lesion site. 2. Materials and methods 2.1. Subjects The study was done with 36 Long–Evans rats, derived from the Charles River Long–Evans strain. The distribution of animals per group was: control rats, n = 12 (six males, six females), rats with postnatal day 10 lesions (Pl0), n = 12, (six males, six females), postnatal day 160 lesions (P160), 0166-4328/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2003.09.026