L. R. JOHNSON, M. HOU, *J. E. LEDOUX;
Ctr Neural Sci, New York Univ, New York, NY.

The lateral amygdala (LA) has been extensively implicated in the neurobiology of conditioned fear paradigms. Norepinepherine (NE), especially its beta receptors, has been implicated in consolidation, reconsolidation and extinction of fear memories, and has been proposed as a potential treatment for PTSD (Berlau and McGaugh, NLM, 2006; Debiec and LeDoux, N, 2005). Despite the psychopharmacological data in animals and the therapeutic potential in humans relatively little is known about the underlying network and cellular mechanism in the LA. The LA receives subcortical and cortical sensory afferents and both have been implicated in conditioned fear. Here we asked whether NE mediates these effects at afferent input synapses, and if so, what mechanism is involved. We recorded evoked field potential (EFPs) following stimulation of thalamic or cortical afferents in vitro in order to screen for network effects. A 15min application of NE transiently inhibited EFPs in both pathways. However inhibition was greater in the cortical path. In the presence of the GABAa antagonist picrotoxin (PTX) inhibition by NE remained in both pathways but was reduced in amplitude. Moreover difference in the effects of NE on the two pathways was eliminated, indicating that GABA networks contribute to the NE effects in LA but that NE regulates the cortical evoked GABA network to a greater extent. A 15min application of the beta adrenergic agonist isoproterenol (ISO) potentiated EFPs in both pathways for more than 2hrs. ISO produced a greater potentiation of the cortical path and this differential was removed by PTX, suggesting that an additional potentiation occurs via a cortical pathway activated GABA network in LA. The beta antagonist propranolol inhibited late LTP in the cortical pathway (also see Huang et al, JN, 2000). We conclude (1) that plasticity in the cortical and thalamic pathway depends on activation of beta adrenergic receptors; (2) that the cortical and thalamic afferents to the LA are regulated in part by distinct GABA networks; and (3) that these networks are subject to control by NE receptors. Thus, both transient inhibition by NE and long lasting regulation of plasticity via beta adrenergic receptors predominates at cortical synapses. In conclusion, NE may regulate memory formation in the LA with both temporal and synapse precision.
Support Contributed By:R01 MH046516;P50 MH058911;K05 MH067048;R37 MH38774

Program No. 370.10/KK28
Poster presentation:Monday, Oct 16, 2006, 8:00 AM - 9:00 AM
Location: Georgia World Congress Center: Halls B3-B5