Long-term Changes In Experience Cause Neurons To Sprout New Long-lasting Connect

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Long-term Changes In Experience Cause Neurons To Sprout New Long-

lasting Connections

http://www.medicalnewstoday.com/medicalnews.php?newsid=45708

Medical Institute researchers have discovered that

neurons in the brains of mice sprout robust new connections when the

animals are adjusting to new experiences. The new connections alter

the circuitry of the brain by changing communication between neurons.

The researchers said their findings aid understanding of how

procedural learning induces long-term rewiring of the brain. This

type of learning is used in mastering skills such as riding a bicycle

or typing on a computer.

Medical Institute (HHMI) investigator Karel Svoboda and

his colleagues reported their findings in the June 22, 2006, issue of

the journal Nature. Other co-authors of the paper included

Holtmaat and Wilbrecht in Svoboda's laboratory at Cold Spring

Harbor Laboratory; and Graham Knott and Egbert Welker at the

University of Lausanne in Switzerland.

Svoboda is one of a handful of researchers in the world who are

pioneering the development of new tools and techniques that permit

scientists to observe the brain as it rewires over a period of weeks

or months. This summer Svoboda will move to HHMI's Janelia Farm

Research Campus where he will pursue neurobiology studies and

projects in optics and microscopy.

In the studies reported in Nature, the researchers used mice that

were genetically altered to produce a green fluorescent protein in

specific neurons in the neocortex, which is a region of the brain

that is known to adapt to new experiences. The researchers followed

the growth of dendritic spines in the region of the neocortex that

processes tactile information from the animals' whiskers. Sensory

information from the whiskers is vitally important for mice as they

navigate their environment. Consequently, a significant portion of

the mouse's brain is devoted to processing input from whiskers.

To monitor changes in neuronal structure visually, the researchers

used a novel technique that Svoboda's team had developed earlier. The

scientists employed laser-scanning microscopy aimed through a small

glass window in the animals' skulls to image changes in fluorescence

that revealed dendritic alterations present on the neurons.

In this most recent experiment, Svoboda's team was looking to see if

persistent changes in connectivity occurred after a long-term change

in experience. They focused on the formation of new long-lasting

spines that indicate robust connections between a neuron's highly

branched dendrites and nearby axons. Dendrites are the input side of

neurons and axons the output side. Spines stipple the surface of

dendrites, like twigs from a branch, and form the receiving ends of

synapses, which are the junctions between neurons where

neurotransmitters are released.

The researchers induced a long-term change in the sensory experience

of mice by trimming the animals' whiskers, selectively cutting some

but leaving neighboring whiskers, in a chessboard pattern. Over time,

this selective grooming caused the animals' neurons to rewire

themselves to adapt to loss of the whiskers - a strategy that reduces

dependence on lost whiskers and enhances input from intact whiskers.

" We knew from previous work that a subpopulation of dendritic spines

appears and disappears over time, but we didn't know the biological

meaning of this process, " said Svoboda. " In these experiments, we

found that over about a month new spines appeared, and in particular

a subset of these new spines stabilized to form new circuits, " he

said.

He said that the researchers were most excited to find that after

this long-term change in experience there were many new spines that

were large, robust and " persistent, " meaning that they remained over

long periods of time. " Under normal conditions, most new spines are

faint and small, and disappear after a couple of days, " said

Svoboda. " What we think they are doing is reaching out and probing

for potential neuronal partners. And while most of them retract, with

novel sensory experience some populations of these new spines make

connections that constitute beneficial new wiring. So those spines

gain bulk and are stabilized as persistent spines. "

In addition to observing the gain and loss of persistent spines, the

researchers also used electron microscopy to examine the new spines

in more detail. That study showed that the new persistent spines

participate in synapses, said Svoboda.

Svoboda said the discovery of experience-dependent, persistent-type

dendritic spine growth has broader implications for understanding

learning. " We think these findings apply to understanding a form of

implicit memory of training-based skills, " he said. " It's the kind of

learning that you can't describe in words, like learning how to play

the piano or to read Braille. It's in contrast to explicit memory,

which is used to remember facts. "

Svoboda said the discovery suggests new ideas for future studies

aimed at understanding the neuronal wiring process in greater detail.

For example, he and his colleagues will study the rewiring of the

animals' brain circuitry as trimmed whiskers regrow, to determine

whether the rewiring can be 'undone' when conditions return to

normal. The researchers also plan more detailed study of the

circuitry itself, to understand the changes in the brain's wiring

diagram caused by spine growth.