| Program#/Poster#: |
914.17/MMM33 |
| Title: |
Exchange protein directly activated
by cAMP (Epac) contributes to the formation of long-term memory for fear
conditioning |
| Location: |
Halls B-H |
| Presentation Time: |
Wednesday, Nov 17, 2010, 1:00 PM - 2:00
PM |
| Authors: |
*H. C. SCHIFF1,
J. P. JOHANSEN1, J. E. LEDOUX1,2;
1Ctr. for Neural Sci., New York Univ., NEW YORK, NY; 2Emotional Brain Inst.,
Nathan S. Kline Inst. for Psychiatry Res., Orangeburg, NY |
| Abstract: |
The lateral nucleus of the amygdala
(LA) is a crucial site of plasticity for Pavlovian fear conditioning. Norepinephrine,
which acts partially through beta noradrenergic receptors (beta-ARs), is
important in the formation of long-term memory and in synaptic plasticity.
Beta-ARs have been implicated in the consolidation of fear learning at least
in part through cAMP-dependent protein kinase (PKA) activation. However,
there are alternate, non-PKA dependent, signaling pathways downstream of
beta-ARs which also participate in memory formation. One such pathway involves
Epac, a guanine nucleotide exchange factor for Rap proteins, which has been
implicated in learning and memory as well as synaptic plasticity. We examined
whether Epac contributes to memory formation for fear conditioning. We hypothesized
that Epac activation during fear learning enhances memory formation because
beta-AR signaling is known to positively modulate fear learning and because
Epac activation has been shown to enhance memory in other learning paradigms.
Because no specific pharmacological inhibitor of Epac is available, we used
a selective Epac activator, 8-pCPT, which does not activate PKA. Rats underwent
Pavlovian auditory fear conditioning in which an auditory tone conditioned
stimulus (CS) was paired with a footshock (US). Rats received three CS-US
pairings. Freezing in response to the CS was then measured 3 hours after
training to assess short-term memory or 48 hours after training to assess
long-term memory. Pre-training infusions of 8-pCPT (0.5µg in 0.25µL)
into the LA potentiated long-term memory but had little effect on short-term
fear memory. In contrast, intra-LA 8-pCPT administered before testing did
not affect expression of a previously learned memory. These results suggest
that Epac is involved in the formation of long-term memory for fear conditioning,
possibly by modulating early consolidation processes initiated during training.
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| Support: |
MH46516
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