Mar 14, 2001 (United Press International via COMTEX) -- Continued production of new neurons in a memory-related region of the adult brain of a mammal -- something long thought impossible -- is essential for at least one kind of retention, scientists report.

The results of the rat study indicate that one day such cells could be added to the brain circuitry as a treatment for a variety of neurodegenerative and developmental diseases, stroke or even spinal-cord injury, they said in the British journal Nature.

Contrary to long-held dogma, there is growing evidence that neurons continue to be produced in the adult mammalian brain in a process called neurogenesis, but until now the role of these newborn cells has remained a puzzle.

The latest research shows adding new neurons to a rodent's hippocampus -- a highly complex region of the brain thought responsible for consolidating memories into permanent storage -- is vital to the kind of memory that involves the timing of learned responses and temporal relationships between events, said lead study author Tracey Shors of Rutgers University in Piscataway, N.J.

"The results support the idea that it might, one day, be possible to add new, fully functional neurons into existing brain circuitry to treat diseases of the nervous system," said Dr. Jeffrey Macklis, associate professor of neurology at the Harvard Medical School in Boston, Mass., who wrote an accompanying commentary.

The new study goes to the heart of the all-important question of whether the new neurons play a crucial role or are subservient to the well-established cells of the neuronal circuitry, he said.

"These results indicate that newly generated neurons in the adult are not only affected by the formation of a hippocampal-dependent memory but also participate in it," Shors said.

Until now, scientists did not know whether the new neurons -- several thousand of which are produced in the rat hippocampus every day -- are involved in memory formation, she said.

"We show that a substantial reduction in the number of newly generated neurons in the adult rat impairs hippocampal-dependent trace conditioning, a task in which an animal must associate stimuli that are separated in time," Shors said. "A similar reduction did not affect learning when the same stimuli are not separated in time, a task that is hippocampal-independent."

"These results suggest that immature neurons in the adult brain are involved and perhaps necessary for the acquisition of new hippocampal-dependent memories about temporal relations or the accurate timing of learned responses, such as during the acquisition of trace memories," Shors concluded.

In trace-conditioning experiments, rats are first trained to associate a sound of a neutral nature -- neither pleasant nor unpleasant -- with a delayed, unpleasant stimulus, such as a gentle stimulation of the eyelid. The animals are then tested to determine whether they react -- by blinking -- to the neutral sound alone. Such reaction indicates they are remembering the unpleasant stimulus. Trace conditioning -- unlike some other types of memory -- depends on the hippocampus and is therefore referred to as hippocampal-dependent.

Using a drug, Shors and team reduced the birth of neurons in the rats' hippocampus. They found that a roughly 80 percent reduction in newborn neurons affected the animals' trace-conditioning memory. However, it had no bearing on another type of memory which does not depend on the hippocampus.

When the researchers restored the normal level of neurogenesis in the hippocampus, the rats recovered their trace-conditioning memory.

"The implication is that the normal level of neurogensis in the hippocampus of adult rats is required for some types of memory that are related to the timing and temporal order of events," Macklis said. "The implication is that new neurons themselves are involved in forming new memories."

The study is the latest in a series of projects focused on uncovering the effects of learning, hormones, seizures, physical activity and the environment on neurogenesis.

Key remaining questions include: What is the connection between stress, a boring environment or depression and reduced neuron births? Does such reduction harm memory and behavior?

"The answers to these questions will be important not only in understanding the role of neurogenesis in the function of the hippocampus but also in the field of brain repair," Macklis told United Press International.

"If the development of immature neurons and precursor cells could be controlled, those cells might replace neurons that are dead or dying, as a result of neurodegenerative disease, developmental disease, stroke or spinal-cord injury, for example."

Studies of songbirds and other species have indicated that neurons are involved in song production and memory and that transplanted immature neurons and precursor cells, called stem cells, can repair to some degree even complex, long-distance connections in the adult brain. Scientists have even been able to stimulate the birth of new neurons in the cerebral cortex of adult mice, a region where neurogenesis does not normally occur.

Scientists are looking into the potential of replacing neurons in the brain and spinal cord of mammals and of controlling the precise development of immature neurons and stem cells so they can supplant the ones that are dead or dying from disease or injury.

"To achieve such precise control over neuronal fate will be extremely complex and difficult. However, for such approaches to even be realistically considered, it is crucial to understand whether newly incorporated neurons can actually play a functional role in already existent nervous system circuitry," Macklis said.

"Equally important, if these approaches are to be truly successful, the newly incorporated neurons must actually be able to function in the existing neuronal circuitry."

"While there has been reason to believe that this goal is reasonable from work in songbirds and other species, this paper sheds important light on these interesting and important questions," he told UPI. "It provides evidence that newborn neurons in the adult mammalian brain actually can contribute critically to the complex behavioral function involved in certain forms of memory formation."

By LIDIA WASOWICZ, UPI Science Writer

Copyright 2001 by United Press International.

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• Neurologic Diseases (General)