Just understanding the chemical
basis and even knowing it is chemical is important in terms of understanding
memory.
I will go a little further. It is very important to be interested in what
you are attempting to remember so that you provide your brain with the
necessary emotional loading needed to actually lock down the memory properly. It is not repetition at all that allows
memory to work well. My guess is that repetition
is actually counterproductive.
That means that successful
learning means coming to class been enthusiastic and leaving your learned
student attitude at the door.
Making memories last
by Staff Writers
Drosophila Orb2 plays an important role in the persistence of memory.
Upon stimulation, Orb2 (shown in yellow) forms amyloid-like oligomers (shown in
red), which are an essential ingredient for the formation of long-term memory.
Credit: Illustration: Nicolle Rager Fuller, Sayo-Art.
Memories in our brains are maintained by connections between neurons
called "synapses". But how do these synapses stay strong and keep
memories alive for decades?
Neuroscientists at the Stowers Institute for Medical Research have
discovered a major clue from a study in
fruit flies: Hardy, self-copying clusters or oligomers of a synapse protein
are an essential ingredient for the formation of long-term memory.
The finding supports a surprising new theory about memory, and may have
a profound impact on explaining other oligomer-linked functions and diseases in
the brain, including Alzheimer's disease
and prion diseases.
"Self-sustaining populations of oligomers located at synapses may
be the key to the long-term synaptic changes that underlie memory; in fact, our
finding hints that oligomers play a wider role in the brain than has been
thought," says Kausik Si, Ph.D., an associate investigator at the Stowers
Institute, and senior author of the new study, which is published in the
January 27, 2012 online issue of the journal Cell.
Si's investigations in this area began nearly a decade ago during his
doctoral research in the Columbia
University
He found that in the sea slug Aplysia californica, which has long been
favored by neuroscientists for memory experiments because of its large,
easily-studied neurons, a synapse-maintenance protein known as CPEB
(Cytoplasmic Polyadenylation Element Binding protein) has an unexpected
property.
A portion of the structure is self-complementary and-much like empty
egg cartons-can easily stack up with other copies of itself. CPEB thus exists
in neurons partly in the form of oligomers, which increase in number when
neuronal synapses strengthen.
These oligomers have a hardy resistance to ordinary solvents, and
within neurons may be much more stable than single-copy "monomers" of
CPEB. They also seem to actively sustain their population by serving as templates
for the formation of new oligomers from free monomers in the vicinity.
CPEB-like proteins exist in all animals, and in brain cells they play a
key role in maintaining the production of other synapse-strengthening proteins.
Studies by Si and others in the past few years have hinted that CPEB's
tendency to oligomerize is not merely incidental, but is indeed essential to
its ability to stabilize longer-term memory. "What we've lacked till now
are experiments showing this conclusively," Si says.
In the new study, Si and his colleagues examined a Drosophila fruit fly
CPEB protein known as Orb2. Like its counterpart in Aplysia, it forms oligomers
within neurons.
"We found that these Orb2 oligomers become more numerous in
neurons whose synapses are stimulated, and that this increase in oligomers
happens near synapses," says lead author Amitabha Majumdar, Ph.D., a
postdoctoral researcher in Si's lab.
The key was to show that the disruption of Orb2 oligomerization on its
own impairs Orb2's function in stabilizing memory. Majumdar was able to do this
by generating an Orb2 mutant that lacks the normal ability to oligomerize yet
maintains a near-normal concentration in neurons. Fruit flies carrying this
mutant form of Orb2 lost their ability to form long-term memories.
"For the first 24 hours after a memory-forming stimulus, the
memory was there, but by 48 hours it was gone, whereas in flies with normal
Orb2 the memory persisted," Majumdar says.
Si and his team are now following up with experiments to determine for
how long Orb2 oligomers are needed to keep a memory alive. "We suspect
that they need to be continuously present, because they are self-sustaining in
a way that Orb2 monomers are not," says Si.
The team's research also suggests some intriguing possibilities for
other areas of neuroscience. This study revealed that Orb2 proteins in the
Drosophila nervous system come
in a rare, highly oligomerization-prone form (Orb2A) and a much more common,
much less oligomerization-prone form (Orb2B).
"The rare form seems to be the one that is regulated, and it seems
to act like a seed for the initial oligomerization, which pulls in copies of
the more abundant form," Si says. "This may turn out to be a basic
pattern for functional oligomers."
The findings may help scientists understand disease-causing oligomers
too. Alzheimer's, Parkinson's and Huntington's disease,
as well as prion diseases such as Creutzfeldt-Jakob disease, all involve the
spread in the brain of apparently toxic oligomers of various proteins. One such
protein, strongly implicated in Alzheimer's disease, is amyloid beta; like Orb2
it comes in two forms, the highly oligomerizing amyloid-beta-42 and the
relatively inert amyloid-beta-40.
Si's work hints
at the possibility that oligomer-linked diseases are relatively common in the
brain because the brain evolved to be relatively hospitable to CPEB proteins and
other functional oligomers, and thus has fewer mechanisms for keeping rogue
oligomers under control.
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