Neuroscience CNS

1. GENETIC MEMORY

2. GENETIC MEMORY
It is always a challenge to be asked to give a presentation to a
group of individuals about a topic to capture their attention,
stimulate their interest, and spark their imagination. Eugenics
and cloning have been topics of science fiction for years,
however, today the topics beong in the area of regulation and
ethics of reality for science and that science is not fiction.

4. Cross Sectional Cut.

5. GENETIC MEMORY
What I would like to discuss with you is some genetic research
that has been ocurring over the last 12 years. Carried out at
Cornell, Columbia, the National Institute of Health, and the
University of Hong Kong. Doctors Barbara Hemstead, Co-Chief
of the Division ofHematology/Oncology in the department of
medicine of Cornell. Dr. Bai Lu of NIH, Dr. Petti Pang, PhD., of
the University of Hong Kong. Dr. Duane Alexander of NIH, and
Eric Kandel of Columbia University.

6. GENETIC MEMORY
What these researchers have deicated the last 12 years of their
research to is the study of memory and the proteins involved in
the making of short term to long term memory. The end result
would be to try and eradicate learning disablities and try to
alleviate the mental deterioration of Alzheimers Disease.

7. GENETIC MEMORY
As quick over-view we know how memories are made we
understand how the proteins and enzymes interact with the
processing of memories. If you will recallthe portion of the brain
linked to memory is the Hippocampus. By sacrificing rodents
and placing electrodes in the Hippocampal slices then
discerning which proteins were present or absent dictated to us
the responsible proteins for memory.

8. GENETIC MEMORY
A single protein known as mBDNF (Mature Brain Derived
Neurotrophic Factor) chemically alters neurons boosting their
ability to communicate with one another.

9. GENETIC MEMORY
Left Temporal view.

10. Hippocampus
Temporal cross section cut.

11. GENETIC MEMORY
The portion of the brain that helps those names get into
memory in the first place, this Hippocampus we are talking
about, is also part of this temporal lobe. But you can't see it
here, because it's an inside fold, not these outside folds you
see above. To see the Hippocampus we'll have to use x-ray
vision. Imagine you could just squint and see right through the
temporal lobe to what's underneath.

12. GENETIC MEMORY
In 1996 it was discovered BDNF fostered changes in cells
indicative of memory. In 1998 Nobel Laureate Dr. Eric Kandel
reported that TPA, (Tissue Plasminogen Activator) was also
involved in long term memory.

13. GENETIC MEMORY
A breakthrough in 2001 with Dr. Barbars Hepstead, MD, PhD.
Deciphered the chemical reaction leading to the formation of
mBDNF, researchers relied on observations of laboratory
phenomenon thought to mirror changes that occur in the brain
when long term memory is formed.

14. GENETIC MEMORY
Neurons communicate via a relay system of electrical impulses
and specialized neurotransmitters are released which bind to
reeceptors on nearby neurons. The recipient neurons then
generate their own electrical impulses and release their own
neurotransmitters. When long term memory is made
researchers believe that neurons gain the capability to transmit
a much stronger electrical impulse than they otherwise would
and thus require much less neurotransmitter.

15. GENETIC MEMORY
Brain Neurons synapsing with one another and communicating
via axons.

16. GENETIC MEMORY
In the first of the experiments NIH researchers found that
treating Hippocampal slices with a compound that prevents
new proteins from being made. Researchers found that protein
synthesis for the formation of long term memory. As expected
applying current to the brain slices failed to bring about LTM
because mBDNF could not be manufactured.
Researchers then applied mBDNF directly to the Hippocampal
slices before applying current. They found that mBDNF
completely restored long term potential. This demonstrated that
mBDNF was essential to memory formation and that mBDNF
was the new protein that Scientist had been searching for that
underlies the long term potential of long term memory.

17. GENETIC MEMORY
In the second of the experiment series Scientist at NIH tested
Hippocampal slices that were genetically incapable of
producing the protein and enzyme needed to produce mBDNF.
As a result the researchers could not induce the long term
potential for long term memory. However, they could induce the
LTP in the brain slices if they first supplied the slices with
mBDNF.
Researchers also discovered that mBDNF could restore long
term potential in brain slices incapable of producing
plasminogen.

18. GENETIC MEMORY
Next the researchers treated plasminogen deficient brain slices
with a form of proBDNF that could not be converted to mBDNF,
once again long term potential could not be induced.
These experiments showed that both plasminogen and TPA
are needed to bring about long term memory potential for the
production of mBDNF.
Entire chemical sequence by which TPA brings about the
formation of mBDNF:
http://www.nichd.nih.
gov/new/releases/conversion_model_image.cfm

19. GENETIC MEMORY
In 2005 Y. Peng Loh, PhD. of NICHD, (National Institute of
Child Health and Human Development) head of cellular
neurobiology research was published.
Specifically this research discovered the enzyme
carboxypeptidase E (CPE), is needed to deliver the early or
inactive BDNF--proBDNF to a special compartment in the
neuron. Once in the neuron compartment the pro form is
converted to the active form mBDNF. Once formed it is
released to the outside of the cell where it binds to receptors on
other neurons to form LTM.

20. GENETIC MEMORY
Dr. Loh explained like other proteins proBDNF is made inside
the endoplasmic reticulum there it travels to the golgi
apparatus. Here the proBDNF binds to the CPE which
protrudes from molecules of lipid. If this process does not occur
pro cannot become mature or active BDNF. These lipid
vesicles travel to the outer membrane where mBDNF is then
released.

21. GENETIC MEMORY
Dr. Loh noted that rodents that were deficient or genetically
incapable of producing CPE could not deliver mBDNF. mBDNF
was not made because the pro form was never delivered to the
vesicles. Instead it leaked out of the golgi apparatus; because
the mice could not make mBDNF the mice were shown to have
poor LTM.

22. GENETIC MEMORY
Do you see what this means? A product in the very near future
could be called "Memory in a Bottle."

23. GENETIC MEMORY
What are we outside of our physical bodies? We are a
collection of thoughts, ideas, concepts, all encompassing and
making memories. Is it such a leap in thinking to believe that
one day science and medicine can extract the patients
memories and place them in an artificial environment. In a
bottle if you will. To be able to do this would enable the
individual to not only prevent memory loss and increase
learning capacity but it would in reality have the person living
forever.
Thank you. Aaron Cusimano, MD