[Abstract Title]. - Society for Neuroscience

294. Gene Expression and Fear Learning
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 294.7/SS47
Topic: F.02.f. Fear and aversive learning and memory
Support: NIH Grant 073949
Title: Identification of genes induced by fear conditioning in the lateral amygdala
Authors: *J. E. PLOSKI, K. PARK, G. E. SCHAFE;
Psychology, Yale, New Haven, CT
Abstract: The amygdala is critical for emotional learning and memory, including Pavlovian fear
conditioning (FC), which is thought to play a critical role in the development of post-traumatic
stress disorder. In recent years, a considerable amount of progress has been made in defining the
cellular and molecular mechanisms of FC. Despite this progress, there still remains a paucity of
information regarding the genes required for long term fear memory formation. This lack of
progress is due, in part, to the relatively small size of the lateral nucleus of the amygdala (LA)
and to relatively small changes in gene expression induced by FC, which leads to difficulties in
unambiguously identifying gene expression changes following fear learning. To circumvent this
limitation, we have adopted a strategy of using microarray technology to initially identify genes
induced by long-term potentiation (LTP) and then to ask whether these genes are regulated in an
associative manner by FC in the LA. LTP is an activity-dependent form of synaptic plasticity
that is the leading candidate for the encoding and storage of long-term memory and, unlike
learning, has the advantage of robustly and unambiguously driving gene expression in learningrelated
regions of the brain. In our experiments, we have chosen to focus on LTP-driven changes
in gene expression in the dentate gyrus, a hippocampal region that exhibits a high cell body
density and in which LTP can be readily and robustly induced. Urethane anesthetized rats were
implanted with a bipolar stimulation electrode into the angular bundle of the perforant path.
Fifteen mins after implantation, rats were given high frequency stimulation (HFS) consisting of
six trains of pulses (400 Hz, 20 msec), delivered at a 10 sec interval and repeated six times at an
interval of 2 min. Low-frequency stimulation (LFS) consisted of six pulses, delivered at a 10 sec
interval, repeated six times with an interval of 2 min, to match the tetanus without inducing LTP.
Thirty minutes following LTP induction, the dentate gyrus was microdissected and global gene
expression analysis was performed using DNA microarrays. We unambiguously identified ~40
genes that were 3 fold or more induced upon LTP induction as compared to controls that
received LFS. To determine if these identified genes were also induced in the LA by FC, we
exposed an additional group of rats to FC consisting of 3 tone-shock pairings. Additional groups
of rats received either three immediate shocks, a procedure that does not support fear learning, or
no stimulation. We then performed qrtPCR on mRNA samples from microdissected LA samples
from each group. This approach has allowed us to identify novel genes induced by FC.
Disclosures: J.E. Ploski , None; K. Park, None; G.E. Schafe, None.