LeDoux Lab 2011 SfN Abstracts

Program#/Poster#:	614.17/WW70
Title:	Mechanisms of β-adrenergic receptor-mediated enhancement of fear conditioning
Location:	Hall A-C
Presentation Time:	Tuesday, Nov 15, 2011, 8:00 AM - 9:00 AM
Authors:	*H. C. SCHIFF1, J. P. JOHANSEN1, J. L. LEDOUX1,2; 1Ctr. for Neural Sci., New York Univ., NEW YORK, NY; 2Emotional Brain Institute, Nathan S. Kline Inst. for Psychiatric Res., Orangeburg, NY
Abstract:	Memory formation for fear conditioning relies on convergent information about the conditioned stimulus (CS) and unconditioned stimulus (US) relayed to lateral amygdala neurons, causing strengthening of CS input synapses, and resulting in a stronger behavioral response to the CS. Learning the CS-US association is thought to depend largely on Hebbian mechanisms and requires NMDA receptors and voltage gated calcium channel activation. However, Hebbian mechanisms mediated by changes in intracellular calcium may not be sufficient to mediate long-term changes in memory without co-activation of modulatory pathways. Indeed, our lab has recently shown that intra-lateral amygdala blockade of β-adrenergic receptors (β-ARs) during fear conditioning (FC) impairs short- and long-term memory (Bush et al, 2010) and that β-AR activation enhances fear memory formation. These results show that neuromodulation is critical in the formation of the long-term memory. We hypothesize that β-ARs recruit PKA and ERK, creating convergent nuclear signaling that compliments Hebbian mechanisms in the formation of long-term fear memories. We examined the signaling pathways recruited by β-ARs in the enhancement of fear memory, focusing on ERK because previous studies show a connection between β-adrenergic signaling and ERK. To determine whether β-adrenergic signaling enhances fear conditioning through ERK phosphorylation we used a weak FC protocol in which rats received 3 pairings of an auditory CS co-terminating with a 0.4 mA footshock US. CS-elicited freezing behavior was measured forty-eight hours after training. This protocol produces a low but reliable level of freezing and allows the detection of whether manipulations enhance long-term fear memory. Prior to behavioral training, rats received intra-lateral amygdala infusions of ISO alone, ISO + SL327 (a MEK inhibitor), SL327 alone, or vehicle. Animals receiving ISO alone had a stronger fear memory for the CS compared with vehicle treated animals and this effect was blocked in animals which received ISO + SL327 before training. In preliminary biochemistry results we have also found that intra-lateral amygdala ISO infusions produce ERK phosphorylation. These results confirm our previous finding that ISO enhances long-term memory for FC and shows that ERK is involved in the β-AR mediated enhancement of long-term fear memory. Because ERK is also phosphorylated by increases in intracellular calcium it may be a convergence point for Hebbian and β-AR mediated signaling during FC.