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Friday, 23 June 2017

23-07-2017 - Must read - Erase Selected Memories; Leave Others Intact ...

Two Aplysia sensory neurons with synaptic
contacts on the same motor neuron in
culture after isolation from the nervous
system of Aplysia. The motor neuron has
been injected with a fluorescent molecule
that blocks the activity of a specific
Protein Kinase M molecule.
Credit: Schacher Lab/Columbia University
Medical Center
Different types of memories stored in the
same neuron of the marine snail Aplysia can
be selectively erased, according to a new
study by researchers at Columbia University
Medical Center (CUMC) and McGill University
and published today in Current Biology.
The findings suggest that it may be possible
to develop drugs to delete memories that
trigger anxiety and post-traumatic stress
disorder (PTSD) without affecting other
important memories of past events.
During emotional or traumatic events, multiple
memories can become encoded, including
memories of any incidental information that is
present when the event occurs. In the case of
a traumatic experience, the incidental, or
neutral, information can trigger anxiety attacks
long after the event has occurred, say the
"The example I like to give is, if you are
walking in a high-crime area and you take a
shortcut through a dark alley and get mugged,
and then you happen to see a mailbox nearby,
you might get really nervous when you want to
mail something later on," says Samuel
Schacher, PhD, a professor of neuroscience in
the Department of Psychiatry at CUMC and
co-author of the paper. In the example, fear of
dark alleys is an associative memory that
provides important information e.g., fear of
dark alleys -- based on a previous experience.
Fear of mailboxes, however, is an incidental,
non-associative memory that is not directly
related to the traumatic event.
"One focus of our current research is to
develop strategies to eliminate problematic
non-associative memories that may become
stamped on the brain during a traumatic
experience without harming associative
memories, which can help people make
informed decisions in the future -- like not
taking shortcuts through dark alleys in high-
crime areas," Dr. Schacher adds.
Brains create long-term memories, in part, by
increasing the strength of connections
between neurons and maintaining those
connections over time. Previous research
suggested that increases in synaptic strength
in creating associative and non-associative
memories share common properties. This
suggests that selectively eliminating non-
associative synaptic memories would be
impossible, because for any one neuron, a
single mechanism would be responsible for
maintaining all forms of synaptic memories.
The new study tested that hypothesis by
stimulating two sensory neurons connected to
a single motor neuron of the marine snail
Aplysia; one sensory neuron was stimulated to
induce an associative memory and the other
to induce a non-associative memory.
By measuring the strength of each connection,
the researchers found that the increase in the
strength of each connection produced by the
different stimuli was maintained by a different
form of a Protein Kinase M (PKM) molecule
(PKM Apl III for associative synaptic memory
and PKM Apl I for non-associative). They
found that each memory could be erased --
without affecting the other
by blocking one
of the PKM molecules.
In addition, they found that specific synaptic
memories may also be erased by blocking the
function of distinct variants of other molecules
that either help produce PKMs or protect them
from breaking down.
The researchers say that their results could be
useful in understanding human memory
because vertebrates have similar versions of
the Aplysia PKM proteins that participate in
the formation of long-term memories. In
addition, the PKM-protecting protein KIBRA is
expressed in humans, and mutations of this
gene produce intellectual disability.
"Memory erasure has the potential to alleviate
PTSD and anxiety disorders by removing the
non-associative memory that causes the
maladaptive physiological response," says
Jiangyuan Hu, PhD, an associate research
scientist in the Department of Psychiatry at
CUMC and co-author of the paper. "By
isolating the exact molecules that maintain
non-associative memory, we may be able to
develop drugs that can treat anxiety without
affecting the patient's normal memory of past
"Our study is a 'proof of principle' that
presents an opportunity for developing
strategies and perhaps therapies to address
anxiety," said Dr. Schacher. "For example,
because memories are still likely to change
immediately after recollection, a therapist may
help to 'rewrite' a non-associative memory by
administering a drug that inhibits the
maintenance of non-associative memory."
Future studies in preclinical models are
needed to better understand how PKMs are
produced and localized at the synapse before
researchers can determine which drugs may
weaken non-associative memories.

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