Learning impairment induced by lesion of the CA1 field of the primate hippocampus: attempts to ameliorate the impairment by transplantation of fetal CA1 tissue

Abstract

Monkeys with bilateral excitotoxic lesion of the CA1 field of the hippocampus were severely impaired at learning visuospatial conditional tasks. This was not a general spatial impairment, because the animals were not impaired on serial spatial reversal, which requires response flexibility in the spatial domain; they were not impaired at learning to choose the position furthest away from a single stimulus, which requires analysis of spatial layout of the test area, and they were not impaired at discriminating between two patterns that differed only in orientation. CA1-lesioned monkeys were impaired at learning a visuospatial conditional task when trials of the two component types "if AA go left" and "if BB go right" were presented according to either a pseudorandom or alternating schedule; but they were not impaired if one component type of trial was presented until three consecutive correct responses were made, followed by the other type of trial, to three consecutive correct responses. In all cases testing continued until a criterion of 27 of 30 consecutive correct responses across both types of trial was achieved. Although this suggests that CA1-lesioned animals are particularly prone to interference effects, they had no difficulty in learning ten concurrent visual discriminations presented against either a uniform background or with each discrimination presented against its own distinctive background, a condition that might reduce interference in unoperated monkeys. Interference following hippocampal damage might occur at a deeper level than stimulus identification such that animals with hippocampal damage may be able to learn about many aspects of different stimuli in parallel but may be unable to learn about multiple related aspects of the same subject matter. Monkeys with grafts of fetal CA1 tissue in the lesioned CA1 field showed significant improvement relative to CA1-lesioned animals on those tasks on which CA1-lesioned animals were impaired, although they remained impaired relative to control animals. This suggests that the grafts had produced some improvement in performance. Grafted monkeys did not differ from unoperated control monkeys or from CA1-lesioned monkeys on those tasks that were not sensitive to CA1 damage. This demonstrates that the grafts did not have an additional deleterious effect on cognitive performance.

Hippocampal Lesion Prevents Spatial Relational Learning in Adult Macaque Monkeys

“…In contrast, studies on the role of the monkey hippocampal formation in spatial learning and memory have resulted in inconsistent results. Although some studies have shown that hippocampal-lesioned monkeys exhibit impaired performance in various spatial memory tasks (Angeli et al, 1993;Beason-Held et al, 1999;Hampton and Murray, 2004;Alvarado and Bachevalier, 2005), others have failed to show any spatial memory impairment (Ridley et al, 1997;Murray and Mishkin, 1998;Malkova and Mishkin, 2003). However, if the monkey hippocampal formation is integrally involved with the processing of spatial relational information, as is the case in rodents, damage to the hippocampal formation should reliably and consistently impair the monkeys' ability to exhibit behavioral strategies dependent on allocentric representations of space.…”

“…For example, whereas several studies have demonstrated that hippocampal-lesioned monkeys exhibit impaired performance in various spatial memory tasks (Angeli et al, 1993;Beason-Held et al, 1999;Malkova and Mishkin, 2003;Hampton and Murray, 2004;Alvarado and Bachevalier, 2005), other studies have failed to show any spatial memory impairment after selective hippocampal lesions (Ridley et al, 1997;Murray and Mishkin, 1998;Malkova and Mishkin, 2003). Nevertheless, electrophysiological studies suggest that the primate hippocampus is involved in spatial learning and memory (Rolls et al, 1989;Ono et al, 1991;Rolls and O'Mara, 1995;Georges-Francois et al, 1999;Hori et al, 2003).…”

Memory for spatial location and object‐place associations are differently processed by the hippocampal formation, parahippocampal areas TH/TF and perirhinal cortex

“…By contrast, the contribution of the nonhuman primate hippocampus to spatial memory has been more difficult to establish. For example, using spatial memory tasks delivered either manually (Wisconsin General Testing Apparatus) or via computer (automated tasks), some studies found spatial memory deficits (Parkinson et al, 1988;Gaffan and Harrison, 1989a,b;Angeli et al, 1993;Gaffan, 1994a,b;Parker and Gaffan, 1997;Beason-Held et al, 1999;Alvarado et al, 2002) but others did not (Ridley et al, 1997;Murray and Mishkin, 1998;Mál-ková and Mishkin, 2003;Belcher et al, 2006). While these discrepant results may reflect whether the hippocampal lesions in these earlier studies encroached or not onto the adjacent parahippocampal areas TH/TF (Málková and Mishkin, 2003;Belcher et al, 2006), three recent studies using selective neurotoxic lesions of the hippocampus have demonstrated severe spatial memory deficits when the animals had to navigate in an environment and forage for food (Hampton et al, 2004;Glavis-Bloom et al, 2006;Lavenex et al, 2006).…”

Spatial conditional discrimination learning in developing rats

“…Conditional cues therefore have properties similar to occasion setters (Miller & Oberling, 1998). Conditional discrimination learning has been well studied in adulthood in a variety of species including rats (Deacon, Bannerman, & Rawlins, 2001;Good, de Hoz, & Morris, 1998;Murray & Ridley, 1999;Sutherland, McDonald, Hill, & Rudy, 1989;Sziklas & Petrides, 2002;Whishaw & Tomie, 1991), monkeys (Ridley et al, 1997;Ridley, Timothy, Maclean, & Baker, 1995), rabbits (Rogers & Steinmetz, 1998), pigeons (Watanabe, 2002), and in human children (Perez-Gonzalez & Serna, 2003) and adults (Fortier et al, 2003;Serna & Perez-Gonzalez, 2003); however, to our knowledge there have been no studies of conditional discrimination learning in developing rats.…”