Effects of selective neonatal hippocampal lesions on tests of object and spatial recognition memory in monkeys

Abstract

Earlier studies in monkeys have reported mild impairment in recognition memory after nonselective neonatal hippocampal lesions. To assess whether the memory impairment could have resulted from damage to cortical areas adjacent to the hippocampus, we tested adult monkeys with neonatal focal hippocampal lesions and sham-operated controls in three recognition tasks: delayed nonmatching-to-sample, object memory span, and spatial memory span. Further, to rule out that normal performance on these tasks may relate to functional sparing following neonatal hippocampal lesions, we tested adult monkeys that had received the same focal hippocampal lesions in adulthood and their controls in the same three memory tasks. Both early and late onset focal hippocampal damage did not alter performance on any of the three tasks, suggesting that damage to cortical areas adjacent to the hippocampus was likely responsible for the recognition impairment reported by the earlier studies. In addition, given that animals with early and late onset hippocampal lesions showed object and spatial recognition impairment when tested in a visual paired comparison task, the data suggest that not all object and spatial recognition tasks are solved by hippocampal-dependent memory processes. The current data may not only help explain the neural substrate for the partial recognition memory impairment reported in cases of developmental amnesia, but they are also clinically relevant given that the object and spatial memory tasks used in monkeys are often translated to investigate memory functions in several populations of human infants and children in which dysfunction of the hippocampus is suspected.

Figure 1

Memory Span Tasks. Examples of one object memory span (A) and one spatial memory span (B). For object memory span (OMS) task, 3-D objects were used and added one at a time at 10-s intervals. Note that for each trial the locations of the objects on the testing board were shuffled so that animal’s performance had to rely on the last object added on the board. For spatial memory span (SMS) task, red checkers pieces were used and added one at a time at 10-s intervals. Animal’s performance relied on selecting the last well (or location on the board) covered. For both tasks, adding an object or a checker piece continued until the animal made an error. + indicates the item rewarded on each trial.

Figure 2

Coronal T1 images through the hippocampus taken one-year postsurgically in a sham-operated monkey (Neo-C-4, left column) and a monkey with neonatal hippocampal lesion (Neo-Hibo-4, right column). Note that, in case Neo-Hibo-4, hippocampal volume reduction is more extensive on the right than on the left, which confirms the percent damage (R: 67.3%; L: 20.3%) that was estimated for that case from the one-week postdurgical FLAIR scan (see Table 1). White arrows point to reduced hippocampal volume as compared to sham-operated control.

Figure 3

Coronal T1 images through the hippocampus taken one-year postsurgically in a sham-operated monkey (C-7, left column) and a monkey with adult hippocampal lesion (Hibo-8, right column). Note that, in case Hibo-8, hippocampal volume reduction is extensive in both hemispheres, which confirms the percent damage (R: 79.7%; L: 98.1%) that was estimated for that case from the one-week postsurgical FLAIR scan (see Table 1). White arrows point to reduced hippocampal volume as compared to sham-operated control.

Figure 4

Photomicrographs through the anterior body of the hippocampus in a normal animal (top row) and two cases with adult onset hippocampal lesions (middle and bottom rows). As estimated from the one-week FLAIR scan (Table 1), the cell loss in case Hibo-7 was extensive on the right, sparing only portion of the uncus, whereas on the left the cell loss was mostly restricted to the CA1 and CA2 subfields. For case Hibo-9, the cell loss was extensive bilaterally in the body of the hippocampus, spanning all CA fields and dentate gyrus, but sparing medial most portions of the uncus. Asterisks indicate region of intense cell loss.

Figure 5

Photomicrographs through the mid-body of the hippocampus in a normal animal (top row) and two cases with adult onset hippocampal lesions (middle and bottom rows). As estimated from the one-week FLAIR scan (Table 1), the cell loss in case Hibo-7 was restricted to the CA1 and CA2 subfields on the right and was moderate in the CA1-CA3 subfields on the left. For case Hibo-9, the cell loss was again extensive bilaterally, spanning all CA fields and dentate gyrus. Asterisks indicate region of moderate to intense cell loss.

Figure 6

DNMS Delay Performance. Mean percent correct on DNMS at delays of 30, 60 and 120-s (100 trials) and 600-s (50 trials) for animals with neonatal (Neo-Hibo) or adult (Hibo) lesions of the hippocampus and their sham-operated controls (Neo-C and C, respectively. Error bars are standard error of the mean (S.E.M.).

Figure 7

Object Memory Span. Mean memory spans for both novel and repeated spans across 10 days of testing for animals with neonatal (Neo-Hibo) or adult (Hibo) lesions of the hippocampus and their sham-operated controls (Neo-C and C, respectively. Error bars are standard error of the mean (S.E.M.).

Figure 8

Spatial Memory Span. Mean memory spans for both novel and repeated spans across 10 days of testing for animals with neonatal (Neo-Hibo) or adult (Hibo) lesions of the hippocampus and their sham-operated controls (Neo-C and C, respectively. Error bars are standard error of the mean (S.E.M.).