Report: Reflections on the 2014

Genetics Conference on Learning

and Memory
The three talks I found the most interesting are: Elizabeth Murchisons talk on
genome analysis of clonally transmissible cancers of Tasmanian devils and dogs,
Sheena Josselyns lecture on neuron selection in forming a memory trace, and
Naoshige Uchidas talk on dopamine reward prediction.
In the first of these talks, a brief history of the Tasmanian devil facial tumour
disease (DFTD) and canine transmissible venereal tumour (CTVT) was presented,
followed by how the results of genome sequencing shed light on the dynamics and
spread of disease. What I found particularly fascinating about this talk was how the
application of DNA sequencing is revealing aspects of population dynamics and
evolution, but with cells rather than individuals. It was also a refreshing success
story of an application of genome sequencing, in contrast to the results of GWA
studies on identifying genes with small effect for complex diseases that was
presented earlier that day.
What I would have liked to know more of are the genetic differences that can
give insights into the differences between the metastatic quality of DFTD versus the
benign quality of CTVT, and between the transmissibility of DVFT, CTVT versus all
other cancers known. Of the many steps required to form a metastasis, the colony
formation and growth steps are unique in metastatic cancer cells compared to
non-metastatic cells. What is so special about DFTD and CTVT that would allow
colony formation and growth when inoculated in another individual? Would it be
possible to take an existing cancer cell or normal cell, and perform targeted
mutagenesis to transform it into a CTVT or DFTD-like state? Another interesting
topic to explore would be the rate of genetic mutation of these two cancers, or
whether the cancers have become relatively genetically stable. If not, then what are
the main mechanisms of genetic instability, and how does it compare to other types
of cancer?
The next two talks do tie into learning and memory. Sheena Josselyn gave an
introduction into her research on how expression levels of CREB influenced neuron
recruitment in formation of a memory trace, and Naoshige Uchida talked about how
the reward prediction error drives learning. Both are fundamental mechanisms of
different aspects of learning and memory. What I got out of these talks was not a
detailed technical understanding of neurobiology, but a more general view of the
logics behind it. I had previously assumed the mammalian brain to be an organ of
vast complexity (which it still is, but in a different way), and that learning and
memory were rather abstract concepts. I found that these lectures de-mystified my
impression of learning and memory, much like what I experienced after learning
about the mechanisms of sight and hearing.

One of the recurring themes throughout the conference was dopamine, which
was mentioned in a variety of contexts. After learning about how dopamine is
involved in learning, memory and disease, I became curious about whether it was
also involved in the mechanism behind interest. Why do people have different
interests, and how do people develop an interested in something? Intuitively, I feel
that interest is developed through positive feedback from our environment,
contributing to a sense of accomplishment, and also a strong curiosity that can be
triggered by different things depending on the individual. This points to the
involvement of memory and reward signalling, which suggests a role for dopamine.
In thinking more about this, I found myself on tangents about some more
psychological concepts. For example, what are the genetic and neurobiological
differences between human personalities, such as introversion versus extroversion?
Studies have shown that extroverted and introverted people have differences in
dopamine signalling in the brain, and even associated certain alleles with
extroversion. In addition, what about the mechanisms behind intelligence? One
measure of intelligence is the efficiency or rate of learning and memory formation,
but there are also less well-defined aspects of intelligence such as creativity. While
the individual circuitry of the processes of learning and memory have been
discussed in detail and modelled, the overarching mechanism of intelligence is still
vague.
It would be fascinating to better understand the pathways that govern our
behaviour, which are influenced by our interests, our personalities, and our
intelligence. These in turn are influenced by nature and nurture. We have studied
nature in some detail, but nurture and the epigenetic effects on neurobiology and
behaviour are only beginning to be studied. It was unfortunate that Isabelle Mansuy
was unable to give her talk on the epigenetic mechanisms of memory control, which
would have provided a fresh perspective.
Overall, the genetics conference on learning and memory has left me the
following impressions:
1. That the technical barriers in studying neurobiology are being broken
down, with single-cell resolution circuitry even possible for mammals
2. That living organisms are really well-designed machines, and there is a
logic existing behind neurobiology regardless of the complexity of the
organism
3. That there are conserved aspects of neurobiological function and
dysfunction across insects, mammals, and humans, in many more ways
than I expected