Paul Worley and his lab have made, and continue to make,
significant contributions to neuroscience. In particular,
his contributions have furthered our understanding of the
molecular mechanisms activated in response to nerve cell
activity.
Worley's lecture centered around a screen looking for genes
that were up- regulated in response to neuronal activity.
This screen resulted in the discovery of an activity dependent
IEG Arc (activity-regulated cytoskeletal associated protein).
Since its initial discovery, the Worley lab's efforts studying
Arc have been fruitful. Using a new technique called catFISH
they were able to view a history of activity in CAl neurons
that had been activated in response to exposing an animal
to specific environments and probing with an Arc antisense
probe.
Animals were exposed to a one environment initiated Arc
mRNA expression in a sub-set of the total neurons in the
CAl. Re-exposing animals to the same environment activated
the very same sub- population of neurons. However, when
animals exposed to one environment were then introduced
to a novel environment, the introduction resulted in an
equivalent size of activated Arc mRNA, but occurred in a
different population of neurons. This provides a glimpse
into how the external environment is represented by a network
of activated neurons within the brain. The catFISH assay
is a breakthrough because this resolution of sub-populations
of neurons within the same region of the brain would not
be possible using the conventional imaging techniques such
as fMRI and PET.
Worley discussed some of the technical limitations of the
assay, mentioning that because the Arc mRNA is degraded
within a half hour, he and his colleagues were restricted
to a very small window of time in which to perform the assay.
However, efforts are underway to use the Arc promoter-which
is activated very quickly in response to neuronal activity-to
control other genes that have a longer half-life. This,
in turn, will allow Worley and his lab to examine a longer
history of the activated neurons.
