Impaired remote spatial memory after hippocampal lesions despite extensive training beginning early in life

Abstract

Damage to the hippocampus typically produces temporally graded retrograde amnesia, whereby memories acquired recently are impaired more than memories acquired remotely. This phenomenon has been demonstrated repeatedly in a variety of species and tasks, and it has figured prominently in theoretical treatments of memory and hippocampal function. A striking exception to the finding of temporally graded retrograde amnesia comes from studies with rodents using spatial tasks like the water maze. In these studies, recent and remote memory were similarly impaired following hippocampal lesions. In contrast to work with rodents, studies of patients with medial temporal lobe lesions, including complete hippocampal lesions, indicate that remote spatial memory can be intact. One difference between studies in humans and studies in rodents is that spatial memory in animal studies is acquired during a limited period of time when the animals are adults. In contrast, the spatial memory studied in humans was acquired beginning at an early age and learning continued for a considerable period of time. We initiated training in a standard water maze immediately after rats had been weaned at 21 days of age and continued training until the rats were young adults (90 days old). Large hippocampal lesions were made 100 days after the completion of training. After recovery from surgery, control rats exhibited good retention on the first retention probe trial, but rats with hippocampal lesions performed at chance. Thus, even after extended training beginning early in life, and with a prolonged training-surgery interval, hippocampal lesions impair performance in the water maze task. Possible reasons for these findings are discussed in the context of the specific performance requirements of the water maze task.

FIGURE 1

Coronal reconstruction showing the largest (striped) and smallest (black) area of damage for rats with hippocampal lesions. The series of sections progress (top to bottom) from anterior to posterior levels. Numbers represent the distance in millimeters posterior to bregma.

FIGURE 2

Acquisition performance. Percentage of time in the training quadrant during the first 30-s probe trial of each day, across the 49 days of training. Rats (n = 16) were given 8 trials each day for a total of 392 training trials for each rat. Dotted line indicates chance performance (chance = 25%). Error bars show SEM.

FIGURE 3

Performance of two rats (1132 and 1128) on three different occasions: at the beginning of training day 1 (T1), training day 10 (T10), and training day 49 (T49). Black circle in the center of the east quadrant indicates the platform location. Letters B and E on each path indicate the location of the rat at the beginning and end of the probe trial, respectively. Numbers below each track indicate the percentage of time the rat spent in the training quadrant on each probe trial. On T1, before any spatial training, neither rat exhibited a preference for the quadrant that contained the platform. On T10, both rats showed a strong preference for the trained quadrant. On T49, neither rat spent much time in the training quadrant during the probe trial. Yet, both paths indicate that, early in the probe trial, each rat swam to the platform location but then quickly left the area and explored the perimeter of the pool. Note also that at the end of the 30-s probe trial (denoted by letter E), both rats were returning to the correct platform location. This pattern of performance was exhibited consistently by all rats beginning about 20 days of training.

FIGURE 4

Retention test. Percentage of time in the training quadrant during three retention probe trials given 14 days after surgery and 114 days after training for control rats (white circles; n = 8) and rats with hippocampal lesions (black squares; n = 8). The control group performed better than the lesion group on all three probe trials. Asterisks indicate above chance performance (chance = 25%, P < 0.05). Error bars show SEM.