Impaired remote spatial memory after hippocampal lesions despite extensive training beginning early in life.
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.
Clark
Robert E
RE
Veterans Affairs Medical Center, San Diego, California, USA. reclark@ucsd.edu
Broadbent
Nicola J
NJ
Squire
Larry R
LR
D000375:Aging / Q000502:physiology; D000648:Amnesia, Retrograde / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D003714:Denervation; D004195:Disease Models, Animal; D006624:Hippocampus / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000502:physiology; D013663:Teaching
Learn Mem. 1994 Sep-Oct;1(3):203-11
10467597
Nature. 1999 Aug 12;400(6745):675-7
10458163
Hippocampus. 1999;9(3):247-54
10401640
J Neurosci. 1999 Feb 1;19(3):1106-14
9920672
Psychol Rev. 1995 Jul;102(3):419-57
7624455
Curr Opin Neurobiol. 1998 Apr;8(2):293-6
9635216
Eur J Neurosci. 1998 Oct;10(10):3295-301
9786224
Science. 2004 Jul 2;305(5680):96-9
15232109
Behav Brain Res. 1999 Dec;106(1-2):97-107
10595425
Nat Neurosci. 2000 Oct;3(10):1044-8
11017178
J Neurosci. 2000 Dec 1;20(23):8853-60
11102494
Hippocampus. 2001;11(1):18-26
11261769
Hippocampus. 2001;11(1):27-42
11261770
Hippocampus. 2001;11(1):50-5
11261772
J Neurosci. 2001 Jun 15;21(12):4505-13
11404438
J Neurosci. 2002 Jun 1;22(11):4663-9
12040072
Brain Res. 2002 Oct 4;951(2):183-90
12270496
Neuron. 2003 Jan 9;37(1):171-80
12526782
J Neurosci. 2003 Oct 29;23(30):9897-905
14586019
J Neurosci. 1993 Apr;13(4):1759-66
8463849
Science. 1992 May 1;256(5057):675-7
1585183
J Exp Psychol Learn Mem Cogn. 1991 Jul;17(4):595-617
1832430
Behav Brain Res. 1990 May 7;38(2):145-54
2363834
Nature. 2004 Oct 7;431(7009):699-703
15470431
Neuropsychologia. 2004;42(12):1619-35
15327930
Q J Exp Psychol B. 1994 May;47(2):129-50
8052726
Behav Neurosci. 1995 Apr;109(2):195-203
7619310
Curr Opin Neurobiol. 1995 Apr;5(2):169-77
7620304
Hippocampus. 2005;15(2):273-80
15523609
Hippocampus. 2005;15(2):260-72
15523608
Nat Neurosci. 1999 Oct;2(10):898-905
10491611