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December 8, 2001          News Morgue Search  www.feat.org/search/news.asp

RESEARCH

Update: Brain Trek

·        New Cells Thrive in Brain’s Learning Center

·        No Evidence Of New Neurons In Adult Primate Neocortex

·        Understanding of How Vagus Nerve Stimulation Treats Epilepsy

·        New Memories Erase Old By Generating New Neurons

 

[We try to track new discoveries about the brain in areas that may have some future bearing on autism and its treatment.  The information in this post is often technical and esoteric: of interest mostly to the scientists and medical professional subscribers and the lay fanatics amongst us on the quest for the “Lorenzo’s Oil” of autism (if this reference escapes you, go see the movie with the same name).  If you decide to delete-key* all of this, your autistic children will probably not suffer for it, and we won’t feel unappreciated. This, like most other research materials we reproduce here, is not required reading and there will be no quiz.  Your final grade is between you and your maker. But I digress…–LS]

·        coinage alert.

 

New Cells Thrive in Brain’s Learning Center

Hippocampus plasticity surprises researchers

 

[By Leslie Pray (lpray@nasw.org) a freelance writer in Leverett,

Mass.]

http://www.the-scientist.com/yr2001/dec/hot_011210.html

1.   T.J. Shors et al., “Neurogenesis in the adult is involved in the formation of trace memories,” Nature, 410:372-5, March 2001.

 

E. Gould, A. Beylin, P. Tanapat, A. Reeves, T.J. Shors, “Learning enhances adult neurogenesis in the hippocampal formation,” Nature Neuroscience, 2[3]:260-5, March 1999. (Cited in 132 papers)

For decades, biologists believed that brain cells didn’t regenerate.  But over the past several years, researchers from a handful of laboratories across the country, including Elizabeth Gould’s lab at Princeton University, proved this opinion to be wrong. Indeed, up to 5,000 new cells are generated in the hippocampus every day, says Tracey Shors, behavioral neuroscientist and associate professor at Rutgers University, and a coauthor on this Hot Paper.

The hippocampus, or hippocampal formation, is a region of the mammalian forebrain involved with memory and learning. For Shors and Gould, it was a logical next step to ask whether this new cell growth in the hippocampus was connected with hippocampus-dependent learning. What they discovered was both expected and surprising: Since the hippocampus is the neurological seat of learning, it made sense that the new cell growth was affected, but researchers didn’t expect the evidence to be so strong.

Tasks and Tests

Shors, Gould, and their collaborators set up behavioral tasks to test the effect of hippocampal-dependent learning on new-neuron generation in an area of the hippocampal formation known as the dentate gyrus. In one test called the Morris water maze, researchers trained rats to use various spatial cues to find a transparent platform in a pool of water. When the platform is submerged, the animals need their hippocampus so they can learn the cues to find it.

But there is also a hippocampal-independent way to train animals:

learning how to find the platform when it’s above the surface is simpler and doesn’t require the hippocampus. Shors and her collaborators compared the results of the two different types of training to see how they affected neurogenesis.

In a second test, the researchers used what’s known as classical eyeblink conditioning to elicit a basic Pavlovian response: the animals hear a tone and then receive stimulation that makes them blink their eyes. This happens repeatedly until the animals learn that the two stimuli are associated and blink when they hear the tone. As with water-maze training, two ways exist to train the animals. One involves the hippocampus, the other does not. Again, researchers compared how the two modes of learning affected new neuronal growth.

Prior to carrying out the tests, researchers injected the animals with a stain (BrdU) that only newly generated cells would absorb. After the tests, the number of BrdU-labeled cells were counted and used as a measure of neurogenesis. In both tests, the researchers found that hippocampus-dependent conditioning increased the survival of newly generated neurons, whereas hippocampal-independent conditioning did not.

Discoveries and New Questions

The researchers found that compared to untrained controls, the number of new neurons that survived were double in rats that had been trained on hippocampus- dependent tasks, but remained the same in animals trained in a hippocampus- independent manner. “In reality, the learning did not generate new cells but rather enhanced the survival of cells that were generated prior to learning,” Shors says. Of the thousands of new cells that are generated in the hippocampus daily, “the vast majority die within weeks,” says Shors. “But there’s something about hippocampus-dependent learning that rescues them from death.”

While their results weren’t unanticipated, says Shors, it was “certainly surprising to obtain such a clear answer. I don’t think either of us expected that learning would have such a unique effect on these cells, that the effect would be so specific to hippocampal-dependent learning.” This study “changes our perspective on how plastic the hippocampus is,” explains Shors, but it doesn’t clarify what the cells are actually doing.

The two women, says Shors, are still trying to find out what role these cells play in hippocampus-dependent learning. In a follow-up study that appeared in Nature this past March,1 the researchers conducted similar conditioning experiments and showed how a reduction in the generation of new neurons in the hippocampus impairs hippocampal-dependent learning. So not only does hippocampal-dependent learning affect the new cells, but the new cells affect learning. They still don’t know what the cells are actually doing, but at least, says Shors, this “gets us one step closer.”

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No Evidence Of New Neurons In Adult Primate Neocortex

http://unisci.com/stories/20014/1207014.htm

Neuroscientists have not found any evidence that adult primates are able to create new neurons in the most sophisticated part of the brain, the neocortex, according to the results of a study published in today’s issue of the journal Science.

The results from scientists at Yale University and the University of Rochester run counter to a widely publicized report two years ago when other researchers reported the first discovery of neurogenesis—formation of new neurons—in the neocortex of adult monkeys.

The new findings, in a study funded by the National Institutes of Health, come from David Kornack, assistant professor of neurobiology and anatomy at the University of Rochester, and his former adviser, neuroscience pioneer Pasko Rakic of Yale.

“As a neuroscientist, oftentimes the first question I’m asked when I meet someone is, ‘How can I get more brain cells?’ I’m as interested in the question as everyone else,” says Kornack. “It’s now apparent that although some parts of the primate brain do acquire new neurons in adulthood, the neocortex is not among these regions.”

For decades, scientists believed that adult humans and other primates such as monkeys are born pretty much with all the nerve cells, or neurons, in the brain that they’ll ever have. However, in the last few years, several scientists equipped with new imaging techniques have reported growth of new neurons in adult primates including monkeys and humans in certain older parts of the brain, such as the hippocampus, which is key to memory, and the olfactory bulb, which is important for smell.

Two years ago, the idea took a giant step forward when researchers reported new neurons growing in the neocortex of adult monkeys. The neocortex—the wrinkled outer layer of the brain—is the most evolved part of the brain, controlling our most sophisticated behaviors such as language and planning.

The birth of new neurons in that part of the brain could have vast implications for human health and for understanding how the neocortex performs its sophisticated duties.

However, in the study published this week in Science, Rakic and Kornack used the most sophisticated cell analysis techniques available and found no new neurons in the neocortex of adult monkeys despite painstaking analysis of thousands of new cells in the neocortex.

The team used two separate molecular markers to key in on candidates for new neurons, then used laser-based confocal microscopy to look closely at every candidate. They found that oftentimes a cell seemed to carry both signals, flagging it as a newly created neuron, but that when the team looked closely, the “new neuron” turned out to be two separate cells, usually one “old” neuron and one newly created cell of a different type, such as a glial cell.

The pair did find new neurons in the hippocampus and the olfactory bulb. And they did find new cells of other types, such as glial cells, in the neocortex. But the pair, who comprised one of the first teams of scientists to discover that new neurons can be made in the hippocampus of adult primates, did not detect a single new neuron in the neocortex, an idea which caused much excitement among neuroscientists two years ago.

One upshot of the new findings, Kornack says, is that scientists should look to mechanisms besides neurogenesis to understand the workings of the neocortex, such as how we learn and store memories over a lifetime. The work could also affect the development of therapies that use adult stem cells to replace neurons lost to brain injury or neurodegenerative diseases such as Parkinson’s or Alzheimer’s.

“If we can find out what allows stem cells in those few restricted

brain regions to continue producing neurons into adulthood, perhaps we can

mimic that magic in other areas of the brain—such as the neocortex—

that can suffer neuronal loss but don’t normally make neurons,” says

Kornack, who left Yale to join the University of Rochester faculty last

year. He is part of the University’s Center for Aging and Developmental

Biology. - By Tom Rickey

 

 

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Understanding of How Vagus Nerve Stimulation Treats Epilepsy

[Seizures are often comorbid with autism.]

http://news.excite.com/news/pr/011206/pa-cyberonics-vns

PRNewswire - A study presented yesterday at the annual meeting of the American Epilepsy Society/American Clinical Neurophysiology Society indicates that seizure control improves in patients with epilepsy when vagus nerve stimulation (VNS) increases blood flow in the thalamic areas of the brain.

VNS causes activation of synaptic activities at multiple sites in the brainstem and both cerebral hemispheres. The results of the study confirm earlier evidence that showed that altered thalamic processing contributes to the anti-seizure effects of VNS.

“The study results are significant because they show that if patients respond to VNS therapy in the short-term they will continue to respond favorably over the long-term,” said Thomas R. Henry, MD, Neurology, Emory University. “In addition, these results also suggest that if patients undergoing VNS therapy show bilateral thalamic activation in the short-term, we can accurately predict long-term seizure control—something that has not been possible up until now.”

The study involved 11 patients with partial epilepsy who were uncontrolled with AEDs and who had complex partial and general tonic clonic seizures. During one year of VNS, seizure control improved in most patients compared to baseline seizure rates, with a reduction of up to 91 percent.

Each patient had brain flow imaging with positron emission tomography

after three months of VNS. Imaging compared VNS-on versus VNS-off states and

showed numerous sites of brain activity with VNS on. Among those sites, only

the right and left thalami (which may manage excitability of the cortex in

people with epilepsy) were significantly associated with greater seizure

reduction.*

“Our study shows that VNS may benefit other blood functions,” stated Henry. “Blood flow activations in frontal cortex and subcortical sites may alter attention, memory and mood. These activations may not serve to control seizures but might benefit depression and memory impairment.”

Nearly 2.3 million Americans are affected by epilepsy, a chronic neurological disorder. Recent studies have shown that nearly 30 percent of people with epilepsy may not respond adequately to drug therapy. VNS is indicated in the United States for seizures in adults and adolescents over 12 years of age with partial onset seizures that are refractory to antiepileptic medication.

About VNS

VNS stimulates the limbic region of the brain that is responsible for mood, motivation, sleep, appetite, alertness and seizures. A stopwatch-sized generator—the Neurocybernetic Prosthesis (NCP) System—implanted just under the skin in the left chest area delivers pre-programmed, mild, intermittent electrical pulses to the left vagus nerve, 24 hours a day.

VNS is safe and effective. VNS has not been reported to cause the type of side effects associated with AEDS (e.g., cognitive dysfunction, liver damage and blood disorders). Common side effects associated with VNS are hoarseness, sore throat, shortness of breath and coughing, all of which typically occur only during stimulation and diminish over time.

VNS with the Cyberonics NCP System was approved in 1997 for use as an adjunctive therapy in reducing the frequency of seizures in adults and adolescents over 12 years of age with medically refractory partial onset seizures. In addition, the NCP System is currently approved for epilepsy in all the member countries of the European Union, Canada, Australia and other markets. VNS with the Cyberonics NCP System was also recently approved for sale in the European Union and in Canada as a treatment of depression in patients with treatment-resistant or treatment-intolerant major depressive episodes including unipolar depression and bipolar disorder (manic depression).

* * *

 

New Memories Erase Old By Generating New Neurons

http://unisci.com/stories/20014/1206014.htm

Scientists have found that existing memories may be erased in our brain by a process that involves the generation of new neurons. This clearance might be important to “make room” for the acquisition of new memories.

The results are reported in today’s issue of Neuron.

The research team, led by Joe Tsien of the Department of Molecular

Biology at Princeton University, generated mice that lack a protein called presenilin-1 throughout much of the brain. Mutations in presenilin-1 are responsible for the majority of cases of early-onset Alzheimer’s disease, but the function of the protein in the context of the normal CNS is poorly understood.

These mice were viable and grew normally, but the researchers observed that after spending time in a rich, stimulating environment filled with diversions and mouse toys, the brains of presenilin-1 mutant mice generated fewer new neurons than the brains of normal mice.

Tsien and colleagues initially thought that this reduced neurogenesis might cause learning deficits, but, after months of testing, none could be detected. The researchers did observe, however, that time spent in an enriched environment generally enhanced the retention of recent learning.

To their surprise, they also found that some newly formed memories were harder to erase in the mice lacking presenilin-1 than in the control mice.

This suggested to the authors that generation of new neurons is important for the memory-clearance process.

Memory retention ordinarily seems like a good thing. However, as Tsien points out, “adding new neurons to existing networks may potentially disrupt, rather than improve, the function of these networks”.

These findings raise a possibility that chronic abnormalities in this clearance process may contribute to the devastating memory disorder associated with Alzheimer’s disease.

In addition, they raise a potential cautionary note about the therapeutic use of neural stem cell transplantation for neurodegenerative disorders.

* * *

 

Reader’s Posts

Parent of 8 yo with PDD-NOS in VA is seeking information on the medications,

Risperdal and Geodan.  Geodan is fairly new and not much info. available

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Teresa has helped many of us over the past decade and now it’s time for us

to help her in return. Donations are tax-deductible. Include memo “Teresa

Binstock’s research fund” on check and make payable to Autism Autoimmunity

Project, Inc. Send to: Autism Autoimmunity Project Inc., c/o Raymond Gallup,

 

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