The Amygdala and Fear Conditioning: Has the Nut Been Cracked?

The foregoing discussion reveals that our understanding of the basic neurobiological mechanisms of aversive learning has advanced considerably. However, there are still a number of issues that remain to be tackled. First, is the amygdala a storage site for conditional fear memories? In favor of this hypothesis, recent data indicate that the amygdala has a long-term role in expressing fear conditioning over time. We have recently found that selective neurotoxic lesions of the BLA, which spared the CE (a critical point given the role of the CE in fear performance), produce deficits in the expression of conditional fear when made up to 28 days after training (Maren et al. 1996xMaren, S, Aharonov, G, and Fanselow, M.S. Behav. Neurosci., in press. 1996; See all ReferencesMaren et al. 1996). Kim and Davis 1993xKim, M and Davis, M. Behav. Neurosci. 1993; 107: 1088–1092Crossref | PubMed | Scopus (40)See all ReferencesKim and Davis 1993 have reported a similar result with electrolytic CE lesions. Hence, these reports are consistent with the storage of aversive memories in the amygdala. In contrast, McGaugh and his colleagues have evidence that the amygdala has a temporary role in the consolidation of aversive memories (McGaugh 1989xMcGaugh, J.L. Annu. Rev. Neurosci. 1989; 12: 255–287Crossref | PubMedSee all ReferencesMcGaugh 1989). Therefore, additional work is required to determine under what conditions the amygdala has an enduring versus a temporary role in fear conditioning.Second, is the amygdala involved in learning, performance, or both? That is, the deficits in both the acquisition and long-term expression of fear conditioning produced by either CE or BLA lesions do not reveal a specific role for these amygdaloid nuclei in either the learning or performance of conditional fear. However, the identification of CS–US convergence in the LA (Romanski et al. 1993xRomanski, L.M, Clugnet, M.C, Bordi, F, and LeDoux, J.E. Behav. Neurosci. 1993; 107: 444–450Crossref | PubMed | Scopus (248)See all ReferencesRomanski et al. 1993), the rapid development of short-latency associative neuronal firing in the LA (Quirk et al. 1995xQuirk, G.J, Repa, C, and LeDoux, J.E. Neuron. 1995; 15: 1029–1039Abstract | Full Text PDF | PubMed | Scopus (483)See all ReferencesQuirk et al. 1995), the selective of effects of intra-amygdala NMDA receptor antagonists on the acquisition of conditional fear (Miserendino et al. 1990xMiserendino, M.J, Sananes, C.B, Melia, K.R, and Davis, M. Nature. 1990; 345: 716–718Crossref | PubMed | Scopus (558)See all ReferencesMiserendino et al. 1990), the discovery of NMDA receptor-dependent LTP in the BLA in vivo (Maren and Fanselow 1995xMaren, S and Fanselow, M.S. J. Neurosci. 1995; 15: 7548–7564PubMedSee all ReferencesMaren and Fanselow 1995), and the selective effects of damage to the human amygdala on fear CRs (Bechara et al. 1995xBechara, A, Tranel, D, Damasio, H, Adolphs, R, Rockland, C, and Damasio, A.R. Science. 1995; 269: 1115–1118Crossref | PubMedSee all ReferencesBechara et al. 1995) favor the amygdala as a learning structure. Nonetheless, these findings do not preclude a role of the amygdala in the performance of fear responses, and the effects of amygdala lesions on innate or unconditioned fear (e.g.,5xBlanchard, D.C and Blanchard, R.J. J. Comp. Physiol. Psychol. 1972; 81: 281–290Crossref | PubMed | Scopus (467)See all References, 1xAdolphs, R, Tranel, D, Damasio, H, and Damasio, A.R. J. Neurosci. 1995; 15: 5879–5891PubMedSee all References) seem consistent with this possibility. Perhaps the amygdala is required for both the learning and performance of conditional fear, functions that may be mediated by the BLA and CE, respectively.Third, does LTP in the BLA underlie the acquisition of Pavlovian fear conditioning and associative neuronal discharges in the amygdala? As discussed in this minireview, there are now a number of provocative findings that suggest a role for LTP in the amygdala in the acquisition of fear conditioning; it is tempting to speculate that LTP is also responsible for the development of conditional neuronal activity in the amygdala during learning. However, there are lessons to be learned from a close examination of other attempts to link synaptic plasticity mechanisms with learning, for example, efforts to link hippocampal LTP and spatial learning. As Barnes 1995xBarnes, C.A. Neuron. 1995; 15: 751–754Abstract | Full Text PDF | PubMed | Scopus (130)See all ReferencesBarnes 1995 has pointed out, what has frequently been taken as strong evidence for a role of hippocampal LTP in spatial learning has later been shown to have limited validity or has been explained as a spurious correlation. In retrospect, this work has demonstrated that the task of linking synaptic plasticity with learning is exceptionally difficult. Thus, caution must be exercised when making claims that LTP in the amygdala underlies fear conditioning. Indeed, considerably more work will be required to understand the extent to which LTP in the amygdala serves as a mechanism for Pavlovian fear conditioning.And, fourth, how do neuronal ensembles in the amygdala encode CSs, and how do these codes translate into learned behavior? Now that we have begun to identify neuronal correlates of aversive learning in the amygdala, important questions for future research are the nature of the ensemble firing patterns that encode CSs in the amygdala and the translation of these ensemble codes into the diversity of fear CRs observed following training. Single-unit recordings in LA have begun to reveal how pairs of neurons in the amygdala might encode CSs (Quirk et al. 1995xQuirk, G.J, Repa, C, and LeDoux, J.E. Neuron. 1995; 15: 1029–1039Abstract | Full Text PDF | PubMed | Scopus (483)See all ReferencesQuirk et al. 1995), but the translation of neuronal firing in the amygdala into behavioral CRs is a problem that has yet to be addressed. Clearly, further detailed physiological investigations of neuronal activity in the amygdala and interconnected structures are required to begin to answer these important questions.Despite these unresolved issues, however, there is general consensus that the neurons in the amygdala are necessary for the acquisition of Pavlovian fear conditioning. The recent and exciting findings discussed in this minireview bring us one step closer to understanding the basic neurobiological processes underlying this important form of behavioral plasticity. And although we have made considerable progress in understanding these mechanisms, there is still much to be done before we crack the brain's almond.