LeDoux Lab 2009 SfN Abstracts
 
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 Epac’s 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