Back in the 1950s, a 16-year-old boy fell off his bike and hit hishead. The concussion knocked him unconscious for a short while.Afterwards he forgot about the accident. But the cranial trauma didn'tforget about him.
Into his 20s, the young man began suffering from severe seizures,diagnosed as temporal-lobe epilepsy. He would have attacks of granmal every day, which resisted all drug therapy.
By the time he was 25 years old, with no lessening of his intractableconvulsions, neurosurgeons decided as a last resort to removesections of the patient's temporal lobes. This area of the cerebralcortex, just above the ears, was already known to be a focus ofepilepsy. It enfolds the hippocampal region of the brain, which theyalso ablated.
"Indeed, the surgery worked," said cognitiveneuroscientist Howard Eichenbaum, "in the sense that it amelioratedthe seizures to a fair extent, and made them drug-controllable. That'sthe good news."
Eichenbaum is a researcher at the Center for BehavioralNeuroscience, State University of New York at Stonybrook.
"The bad news," he told BioWorld Today, "was that this patientafterwards had a very severe amnesia, or memory deficit. Essentially,he was unable to learn anything new, albeit he had his old memoryintact, of things he had learned in his childhood. Knowledge of theEnglish language, and so on, but nothing new."
This historic surgical experiment has never been done again inpeople. But besides helping that patient, who has been famous eversince, it established the hippocampus as one important locus ofmemory in the brain.
Far more frequent than blows on the head as a cause of memory lossis of course the phenomenon of aging. "This structure, thehippocampus," Eichenbaum observed, "is known to be compromisedin aging people. It's very much implicated in senile dementias,particularly Alzheimer's disease."
Eichenbaum is senior author of a paper in the current Nature, datedJan. 18, 1996, which, he said, "describes a brand new behavioral testto try out drugs that might improve memory in animals who aredeficient because of deterioration due to aging, or damage such ascaused by oxygen deprivation."
His article bears the title: "Conservation of hippocampal memoryfunction in rats and humans."
Learning And Remembering, Rodent Style
Rats, whether negotiating mazes or swimming in strangesurroundings, are the favorite animal subjects of cognitiveneuroscientists. But the kind of memory these sharp but limitedrodents display in such laboratory tests is based on rote repetition ofspatial learning, rather than the subtle inferences that humans use inremembering things.
Eichenbaum's Nature paper reports a test system he devised to morenearly copy in rats the declarative memory that humans use. Bydeclarative memory, he means "recalling facts and events of everydaymemory that occur all the time, and can be consciously recollectedand used."
In human memory testing, subjects may typically hear dictated lists ofpaired words unrelated as to meaning _ for example, army/table orbook/cloud. Then, when one word is repeated, they try to rememberthe other one.
In Eichenbaum's rats, odors replace words. "We exploited the fact,"he said, "that rats are terrific in using odors to guide themselvesaround. If you give them smelly stimuli they like to deal with, theycan learn things incredibly rapidly."
His test animals confront pairs of round clear plastic cups half full ofsand mixed with scented rat chow. From each emanates a differentspicy spell _ cocoa, turmeric, coffee, salt, onion, English breakfasttea _ all new and exciting thrills to the rats' olfactory nerves.
"Smells, in a sense, have a special access to the memory system ofhippocampus and temporal lobe," Eichenbaum explained, becausethere are simply fewer way-stations between the input stimuli of theolfactory sense and the hippocampus."
By digging down through the pungent mixture, a rodent discovers atthe bottom a tasty "reward" morsel that makes his effort worthwhile.Varying the cups two at a time measures the animal's recall.
Half of the rats in the experiment are knockout animals whosehippocampi have been deleted by a precision-guided neurotoxininjected through the skull. The other half are controls, injected with adry needle to imitate the cerebral surgery.
Recruiting Rats To Test Memory Drugs
After the rodents complete their final declarative memory exams, alltheir hippocampus-ablated brains go under the microscope. "Whatone sees," Eichenbaum said, "is a very shriveled remnant; all cellsthat make up the hippocampal bulk are gone. Left behind are themajor axonal tracts that pass through that area, hanging in there."
The animals with neurotoxin-damaged hippocampi, Eichenbaumcontinued, were still able to learn simple associations between odorsand food rewards, but they couldn't extrapolate from theseassociations to draw higher-level inferences. The control animalswith intact hippocampi, could.
"Often in aging, especially Alzheimer's disease, what happens is youhave a loss of the cholinergic system, which compromises thefunction of the hippocampus," Eichenbaum said. "This creates a lossof memory function similar to what we see in these rats, in whichthere is a more direct and explicit source of damage."
That phenomenon, Eichenbaum suggested, "should be of interest tothe whole pharmaceutical and biotech industry. For them the questionwould be: `Are there drugs you can use to help the remains of theaged or damaged hippocampus to work better?' Say, a compound thatmay influence acetylcholine in some way. Of course you'd want totest it out." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.