A brain-damaged patient, known to generations of medical studentsas "H.M.," kept a daily diary. But instead of recording events day byday, he jotted down every event in his life the moment it happened.
This was not a mental aberration, or a nervous tic, but the urgent needto remember.
As neuroscientist John Dani, at Baylor College of Medicine, inHouston, recalled: "The main layer of neurons in patient H.M.'shippocampus was severely damaged. He had to take notes constantlyof what he was doing, so the next day when he woke up, he had somelife history. Otherwise, he remembered his early past, when he was alittle kid, but couldn't lay down new memories."
The hippocampi, Dani's focus of research, are a bilateral pair ofconvoluted, seahorse-shaped regions below the brain's cerebralcortex. They manage the transmission and storage of memory andlearning.
A lack of oxygen to the brain for a period of time is one cause ofhippocampal impairment, as its neurons are very susceptible to suchischemia.
Dani is senior author of a paper in today's Nature titled:"Hippocampal transmission enhanced by low concentrations ofnicotine." In it he states that "Nicotine obtained from tobacco canimprove learning and memory on various tasks and has been linked toarousal, attention, rapid information processing, working memory,and long-time memories that can cause craving years after someonehas stopped smoking."
In undertaking this study, Dani told BioWorld Today, "We weremotivated less to find out about what nicotine from cigarettes isdoing, and more to find out what acetylcholine, the naturalneurotransmitter in the brain, does when it interacts with the samereceptors that the drug nicotine interacts with."
In particular, he added, "how the nicotinic acetylcholine receptorswork in a part of the brain that's very important for learning andmemory, namely, the hippocampus."
Dani pointed out that the hippocampus is rich in neurons that releaseacetylcholine, one of the brain's main neurotransmitters. Moreover,"work from our own lab, and others, found that that area of the brainhas many nicotinic receptors, but nobody had any idea what theywere doing."
Dots And Dashes In The Brain
He added: "We now know, as we report in Nature, that they play animportant role." He compares that role to transmission of a messageby Morse code's dots and dashes. "Imagine neurons sendingelectrical activity, trying to pass along information," he said. "If theline were getting interference, if we had a noisy connection, youwouldn't hear every dot and every dash, so we wouldn't have perfectcommunication.
"What acetylcholine does, we believe, is work through the nicotinicreceptors to help the fidelity of the communication, so the signalbecomes more faithfully passed along from synapse to synapse, andmore reliable."
Dani emphasized the precision of this transmission in the normalbrain. "Those neurons go to very precise locations in thehippocampus, and release acetylcholine to open up those nicotinicreceptors.
"But nicotine on the other hand, when you smoke it," he went on,"goes everywhere in the body. It's a little bit like comparing abricklayer who's putting bricks on your front porch very precisely,and then another guy who comes and just dumps a dump-truck full ofconcrete."
Dani and his co-authors have developed a method by which "we wereable to study one little ending of a neuron in a synapse, and provethat the nicotinic receptors were at those endings and could beactivated by low levels of nicotine, in the concentration range that asmoker would use."
He added that "Nicotine from smokeless tobacco would be the sametype as from smoke. If you had chewing tobacco in your mouth, thenicotine would go all over your body. All areas of your brain _ notjust precise places in the hippocampus _ would experience thisnicotine."
(Dani's nicotine research is supported by the National Institutes ofHealth and by the Smokeless Tobacco Research Council Inc., basedin New York.)
His group now is beginning to explore nicotine's effect on a differentpart of the brain, that's involved in sensations of pleasure and reward,and of addiction.
"These are zones of the brain," he observed, "where we know thatcocaine and amphetamines act. There are some indications thatnicotine may act in these same areas." He cited specifically theventral tegmentum, which projects to the nucleus accumbens, deepdown in the brain. (See BioWorld Today, June 20, 1996, p. 1.)
The Alzheimer's Disease Connection
"Our work may not directly lead us to speculate about nicotineaddiction, because we haven't yet studied those areas. But we didstudy a part of the brain that's very important for memory, and weknow that in Alzheimer's Disease (AD) there are memoryimpairments, which correlate with those neurons that releaseacetylcholine."
One of the many things that happen early on in AD," Dani continued,"is that these neurons, which project to different parts of the brain, inparticular to the hippocampus, and release acetylcholine, are amongthe first neurons that are impaired. If our findings are correct, thenwhat those neurons do is help the fidelity of the signal transmission.Then the logical stretch to AD makes some sense."
He went on: "We think this fidelity impairment in the hippocampuswould be one component of the memory problems that an AD patientexperiences, such as: What day of the week is it? What room of thehouse are you in? Do you remember your nurse?"
Alzheimer's disease research got an unexpected boost from nicotinein this week's issue of Biochemistry, dated Oct. 22, 1996. Thereport's title tells its whole story: "Nicotine inhibits amyloidformation by the b-peptide." Its author is biochemist MichaelZagorski of Case Western Reserve University in Cleveland.
"The brains of patients with AD," his paper pointed out, "contain anabundance of amyloid plaques containing the b-peptide." Zagorskiundertook his investigation in response to "recent reports of aninverse relationship between the risk of AD and cigarette smoking."(See BioWorld Today, March 2, 1995, p. 3.) n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.