LeDoux Lab 2009 SfN Abstracts |
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Program#/Poster#: | 479.26/FF127 |
Title: | Epac is involved in thalamo-amygdala LTP induction |
Location: | South Hall A |
Presentation Time: | Monday, Oct 19, 2009, 2:00 PM - 3:00 PM |
Authors: | *H. C. SCHIFF1, C. CUNHA3, P.
ASKALSKY1, J. E. LEDOUX2,4; 1Ctr. for Neural Sci., 2Ctr. for Neural Sci. and Dept. of Psychology, New York Univ., New York, NY; 3Faculdade de Ciencias, Univ. do Porto, Porto, Portugal; 4Emotional Brain Inst. Labs, Nathan Kline Inst., Orangeburg, NY |
Abstract: | The amygdala is a crucial site of plasticity
for Pavlovian fear conditioning. Norepinephrine (NE) has been implicated
as important for modulating the consolidation of memory and synaptic plasticity,
at least in part through cAMP-dependent protein kinase (PKA) activation
or inhibition. Indeed, behavioral studies of fear conditioning show that
inhibitors of PKA disrupt long-term memory (LTM), but leave short-term memory
(STM) intact. Recent behavioral work shows that pre-training beta-adrenergic
(ß-AR) blockade in the lateral amygdala (LA) disrupts both STM and
LTM for fear conditioning. This is inconsistent with the traditional view
that NE, via PKA, only affects LTM. We explored this discrepancy by examining
the intracellular signaling pathways mediated by ß-AR activation during
LTP induction. Specifically, we examined the role of exchange protein directly
activated by cAMP (Epac), which is a guanine nucleotide exchange factor
for RAP proteins and has recently been linked to intracellular pathways
involved in learning and memory. The signaling pathway initiated by Epac
activation is independent of PKA activation, as it is directly activated
by cAMP. The present experiments examined the involvement of ß-AR activation and Epac in LTP induction at thalamic input pathways to the LA in a whole-cell patch clamp paradigm. LTP induction consisted of 3 trains of 40Hz tetanus stimulation in the presence of picrotoxin (PTX). Initial experiments assessed the effects of propranolol, applied before LTP induction, on the response of the LA cells to thalamic pathway stimulation for 40 minutes. Results showed that the LTP induction protocol potentiated EPSPs during the last 8 minutes in controls slices, but not in slices treated with pre-induction propranolol. To test whether Epac activation plays a role in ß-AR-dependent LTP, we exposed the slice to a selective Epac activator 8-pCPT (100uM 8-(4-Chlorophenylthio)-2'-O-methyladenosine-3', 5'-cyclic monophosphate sodium salt) during LTP induction. Thus, the slice is exposed to PTX, propranolol, as well as 8-pCPT. In these conditions, the response during the last 8 minutes is significantly potentiated to about 119% of the baseline response. Experiments examining the locus of Epacs effects are currently being undertaken by dissolving 8-pCPT in the internal solution. Thus, these experiments will reveal whether Epac is acting at the level of the single cell vs. within the LA circuitry. Our result suggests that Epac contributes to LTP induction in the thalamo-LA pathway. |
Support: | NIH Grant R37 MH038774 |
NIH Grant P50 MH058911 | |
NIH Grant R01 MH046516 | |