COMPLETE SPARING OF SPATIAL LEARNING FOLLOWING POSTERIOR AND POSTERIOR PLUS ANTERIOR CINGULATE CORTEX LESIONS AT 10 DAYS OF AGE IN THE RAT C. L. R. GONZALEZ, I. Q. WHISHAW AND B. KOLB* Canadian Centre for Behavioural Neuroscience, University of Leth- bridge, 4401 University Drive, Lethbridge T1K 3M4, AB, Canada Abstract—Neonatal posterior cingulate cortex lesions spare the spatial deficits that characterize adult lesions. The present experiments examined the possibility that the ante- rior cingulate cortex mediates the spared spatial behavior. Rats were given bilateral lesions of the posterior cingulate cortex or anterior plus posterior cingulate cortex on postna- tal days 4 (P4), 10 (P10), or in adulthood (P120). All groups were tested for spatial learning on the Morris place task in adulthood. Adult animals were impaired on place learning relative to controls whereas place learning was spared in all the neonatal groups and sparing was complete in the group receiving day 10 lesions. The results are discussed in relation to neural mechanisms, including fiber rerouting, synaptic changes and generation of new neurons, that may mediate spared spatial following neonatal posterior cingulate cortex lesions. Also discussed is evidence indicating that the neo- natal brain, especially the day 10, has a special ability to compensate for injury. © 2003 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: cingulate cortex, neonatal brain injury, plasticity. The posterior cingulate cortex makes extensive reciprocal connections with neocortical and limbic structures (van Groen and Wyss, 1990; Olson and Musil, 1992). In both humans and rats damage to posterior cingulate cortex produces impairments in spatial behavior suggesting that the cingulate cortex, or some of its connections, plays a pivotal role in spatial behavior (e.g. Warburton et al., 1998; Harker and Whishaw, 2002; Sutherland et al., 1988; Whi- shaw et al., 2001; Vogt, 1983). Surprisingly, if similar le- sions are produced in neonatal rats, there is significant functional sparing (Gonzalez et al., 2002; Kolb and Whi- shaw, 1991). This finding of neonatal sparing suggests either that some pathway that normally courses through the cingulate cortex finds an alternate route following infant injury, or that some other structures can substitute for cingulate cortex following infant but not adult injury. A possible candidate structure that may substitute for missing cingulate cortex after neonatal injury is the anterior cingulate or medial frontal cortex. Injury to the anterior cingulate cortex in adult rats also produces impairments in spatial behavior (for reviews, see Kolb, 1984; Kolb et al., 2001), and in addition neonatal medial frontal cortex le- sions also spare spatial behavior when the rats are tested in adulthood (Kolb, 1987; Kolb et al., 1987; Kolb and Nonneman, 1978). It is not known whether the spatial functions of anterior and posterior cingulate cortex are related or separate. Nevertheless, it is possible to specu- late that anterior and posterior cingulate cortex can sub- stitute for each other to mediate spatial behavior if lesions are produced in infancy but not if they are produced in adulthood. The primary goal of the current study was to test the idea that medial frontal cortex mediates the sparing of function that follows neonatal posterior cingulate cortex lesions. Rats received either posterior cingulate cortex lesions in infancy or combined posterior cingulate cortex lesions plus anterior cingulate cortex lesions. Because there is evidence showing that damage to frontal, motor, parietal, or occipital cortical areas of rats around 10 days of age is associated with extensive functional recovery in adulthood (for reviews, see Kolb, 1995; Kolb and Whi- shaw, 1989; Nonneman et al., 1984), one group of rats received neonatal lesions at 10 days of age. Because this same literature shows that injuries in the first few days of life or in adulthood do not lead to similar extensive recov- ery, a second group of rats received neonatal lesions at 4 days of age. Both groups were compared in adulthood to rats that had received similar lesions in adulthood and to appropriate control groups that received no lesion. All an- imals were tested on the Morris place task and probe trial, which has been a primary measure of spatial function in rats that have received cingulate cortex lesions. EXPERIMENTAL PROCEDURES Subjects Fifty Long-Evans rats were used in this study. Nineteen (10 males, nine females) received bilateral lesions of the posterior cingulate cortex and 19 rats (10 males, nine females) received lesions of the entire midline cortex. Posterior cingulate cortex removals, which included areas RSA and RSG (Zilles, 1985) bilaterally, were per- formed at the following ages: postnatal day 4 (P4; three males, two females), P10 (three males, three females) or P120 (four males, four females). Animals with the anterior and posterior cingulate cortex lesions had areas CG1, CG2, CG3, RSA, and RSG (Zilles, 1985) removed bilaterally at the same ages de- scribed above with the same distribution of subjects per group respectively. Twelve rats (six males, six females) served as sham- operated controls. To simplify the analysis, the posterior cingulate and complete midline lesion group will be compared with the control group separately. Behavioral testing began at 120 days of age for the neonatal-lesion animals and 160 days of age for the *Corresponding author. Tel: +1-403-329-2405; fax: +1-403-329- 2775. E-mail address: kolb@uleth.ca (B. Kolb). Abbreviations: P, postnatal day; RSA, rhythmical slow activity. Neuroscience 122 (2003) 563–571 0306-4522/03$30.00+0.00 © 2003 IBRO. Published by Elsevier Ltd. All rights reserved. doi:10.1016/S0306-4522(03)00295-1 563