| LeDoux Lab 2012 SfN Abstracts |
|---|
| Program#/Poster#: | 603.02/EEE5 |
| Title: | Mechanisms of β-adrenergic signaling in acquisition and consolidation of defense conditioning |
| Location: | Hall F-J |
| Presentation Time: | Tuesday, Oct 16, 2012, 9:00 AM -10:00 AM |
| Authors: | *H. C. SCHIFF1,
J. P. JOHANSEN2, R. M. SEARS1, J. E. LEDOUX1,3;
1Ctr. for Neural Sci., New York Univ., NEW YORK, NY; 2RIKEN Brain Sci. Inst., Wako, Japan; 3Emotional Brain Inst., Nathan Kline Inst., Orangeburg, NY |
| Abstract: | Associative learning of
defense conditioning (so called fear conditioning) depends on Hebbian and
neuromodulatory processes (Johansen et al, 2011). In defense conditioning
memory formation relies on convergent information about the conditioned
stimulus (CS-an auditory tone) and unconditioned stimulus (US-a mild shock)
relayed to lateral amygdala (LA) neurons, causing strengthening of CS synapses
and resulting in a stronger behavioral response to the CS. Defense conditioning
is impaired when β-ARs are blocked with the antagonist, propranolol, before
training but not when propranolol is administered immediately after training,
showing a role of β-ARs in acquisition, but not consolidation. Likewise,
activating β-ARs with the agonist, isoproterenol (ISO), enhances memory
when it is administered before training, but not immediately after (Caparosa
et al, 2010). We investigated the mechanism of β-AR-mediated enhancement in memory by looking at the downstream kinases activated by β-ARs. We focused on extracellular signal-regulated kinase (ERK) because previous studies show a connection between β-adrenergic signaling and ERK. Furthermore, ERK is necessary for long term memory (LTM) for defense conditioning, though it is not required for short-term memory (STM). Animals were trained on weak defense conditioning (3 pairings of an auditory CS co-terminating with a 0.4mA footshock US). Animals received intra-LA infusions of ISO alone, ISO + SL327 (an indirect inhibitor of ERK), SL327 alone, or vehicle before training. While animals receiving ISO alone had a stronger memory for the CS at the LTM test, this memory enhancing effect was completely abolished when ERK phosphorylation was blocked in the ISO + SL327 group. However, blocking ERK phosphorylation had no effect on the short term memory enhancing effects of β-AR stimulation as animals receiving ISO alone or ISO + SL327 both had enhanced freezing compared to the vehicle group at STM. Importantly, blocking ERK phosphorylation had no effect on weak fear memory formation on its own. These results strongly suggest that β-ARs enable LTM through ERK activation, but they recruit an alternate signaling pathway for permitting STM. We propose that one role of β-AR signaling is to converge with Hebbian signaling onto ERK and other second messengers, leading to memory formation. Biochemical studies are currently underway to determine the second messenger pathways involved in memory formation for defense conditioning. |
| Support: | NIMH R01 MH46516 |