| Program#/Poster#: |
479.24/FF125 |
| Title: |
Pre-training exposure to novelty
enhances performance in memory-impaired individuals |
| Location: |
Washington Convention Center: Hall A-C
|
| Presentation Time: |
Tuesday, Nov 18, 2008, 9:00 AM -10:00
AM |
| Authors: |
*K. K. COWANSAGE, E. KLANN, J. E. LEDOUX;
Ctr. Neural Sci., New York Univ., New York, NY |
| Abstract: |
In the typical individual, fear memory
formation is an adaptive process that enables the organism to respond to
stimuli that predict harm. Although the majority of both humans and rodents
express moderate levels of fear in response to mild aversive stimuli, a
subset of individuals within outbred populations have a pre-existing enhanced
or impaired ability to retain long-lasting emotional memories. Because these
deviant behavioral phenotypes may be associated with emotional and cognitive
pathologies at either end of the spectrum, it is of clinical importance
to understand the biological mechanisms that modulate memory intensity.
Considerable work indicates that phosphorylation of the transcription factor,
cAMP response element binding protein (CREB), which regulates the expression
of numerous genes involved in activity-dependent neuronal plasticity, may
influence neuronal excitability and participate in the gating of memory
strength (Han et al, 2007; Marie et al 2005; Yuan et al 2003). Here we have
used Western blots to demonstrate that outbred Sprague Dawley rats expressing
above-average memory show higher basal levels of CREB phosphorylation in
the lateral amygdala (LA) than rats expressing below-average memory. We
then asked whether these stable phenotypic extremes could be specifically
manipulated by priming the machinery involved in amygdala-dependent memory
formation prior to fear conditioning. Unlike typical manipulations of memory
where the goal is to change the group mean, our objective was to specifically
shift extreme individuals toward the average. To do this, we used a paradigm
modeled after that applied in the behavioral tagging study by Moncado &
Viola (2007), where pre-training exposure to spatial novelty effectively
converted subthreshold learning to memory without enhancing suprathreshold
learning. We show that a similar manipulation prior to fear conditioning
induces CREB phosphorylation in the LA and leads to a population wide shift
in the phenotypic distribution, where previously poor-consolidators now
demonstrate average performance at test of long-term memory. Future work
will aim to pharmacologically mimic this effect and ultimately provide a
specific mechanistic basis for the observed behavioral differences. |
| Support: |
NIH Grant F31MH083472-02 (KKC) |
|
NIH Grant NS034007 (EK) |
|
NIH Grant NS047384 (EK) |
|
K05 MH067048 |
| NIH Grant P50 MH058911 (JEL) |