Does the basolateral amygdala store memories for emotional events

In his recent article Stephen Maren advances LTP in the basolateral amygdala (BLC) as a mechanism for encoding and storing emotional memory1xLong-term potentiation in the amygdala: a mechanism for emotional learning and memory. Maren, S. Trends Neurosci. 1999; 22: 561–567Abstract | Full Text | Full Text PDF | PubMed | Scopus (276)See all References1. He asserts that: (1) ‘fear memories are formed and stored in the basolateral amygdala’; and that (2) ‘fear conditioning induces LTP in the amygdala’. The first postulation has two major problems. First, it does not acknowledge many studies that have seriously questioned the role of the BLC as a permanent repository of memories for emotional events2xIs the amygdala a locus of ‘conditioned fear’? Some questions and caveats. Cahill, L. et al. Neuron. 1999; 23: 227–228Abstract | Full Text | Full Text PDF | PubMed | Scopus (180)See all References2. Second, in interpreting the data presented, the author relies on assumptions that are not supported by existing data.Several studies provide strong evidence for spared memory of classical conditioning in rats with BLC lesions. A day after context–footshock conditioning, rats with permanent or temporary BLC lesions display impaired freezing compared with sham control rats, yet they selectively avoid a place previously paired with footshock3xComplementary roles for the amygdala and hippocampus in aversive conditioning to explicit and contextual cues. Selden, N. et al. Neuroscience. 1991; 42: 335–350Crossref | PubMed | Scopus (370)See all References, 4xBasolateral amygdala is not critical for cognitive memory of contextual fear conditioning. Vazdarjanova, A. and McGaugh, J.L. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 15 003–15 007Crossref | Scopus (116)See all References, 5xBasolateral amygdala infusions of lidocaine disrupt both acquisition and consolidation of memory for contextual fear conditioning. Vazdarjanova, A. and McGaugh, J.L. Soc. Neurosci. Abstr. 1998; 24: 1684See all References. Additionally, BLC lesions do not disrupt conditioned suppression, which also requires an association between neutral and aversive stimuli6xDifferent types of fear-conditioned behaviour mediated by separate nuclei within amygdala. Killcross, S. et al. Nature. 1997; 388: 377–830Crossref | PubMed | Scopus (480)See all References6. Furthermore, rats with BLC lesions show savings when retrained compared with naove lesioned rats7xOvertraining does not mitigate contextual fear conditioning deficits produced by neurotoxic lesions of the basolateral amygdala. Maren, S. J. Neurosci. 1998; 18: 3088–3097PubMedSee all References, 8xAmygdala lesions do not impair shock-probe avoidance retention performance. Lehmann, H. et al. Behav. Neurosci. 2000; 114: 107–116Crossref | PubMedSee all References or with lesioned rats that received training in a different environment9xSee all References9. In at least two studies4xBasolateral amygdala is not critical for cognitive memory of contextual fear conditioning. Vazdarjanova, A. and McGaugh, J.L. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 15 003–15 007Crossref | Scopus (116)See all References, 9xSee all References, spared memory was evident in rats with nearly complete (>98%) BLC lesions, suggesting that spared tissue is not likely to account for the memory savings. Additionally, the deficits in some indices of learned fear, such as freezing, potentiated startle and hypoalgesia, following BLC lesions could be deficits in behavioral expression, that is, an inability of lesioned rats to perform these behaviors in response to fearful stimuli, both unlearned and learned10xNeural systems for the expression of hypoalgesia during nonassociative fear. Bellgowan, P.S. and Helmstetter, F.J. Behav. Neurosci. 1996; 110: 727–736Crossref | PubMedSee all References, 11xDouble dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear. Walker, D.L. and Davis, M. J. Neurosci. 1997; 17: 9375–9383PubMedSee all References, 12xEffects of regional amygdaloid lesions on flight and defensive behaviors of wild black rats (Rattus rattus). Kemble, E. et al. Physiol. Behav. 1990; 48: 1–5Crossref | PubMed | Scopus (43)See all References, 13xEffects of aspiration versus neurotoxic lesions of the amygdala on emotional responses in monkeys. Meunier, M. et al. Eur. J. Neurosci. 1999; 11: 4403–4418Crossref | PubMed | Scopus (127)See all References, 14xInnate snake fear in rhesus monkeys: role of the amygdala. Nelson, E. et al. Soc. Neurosci. Abstr. 1999; 25: 2151See all References, 15xBasolateral amygdala lesions disrupt both unconditioned and conditioned freezing. Vazdarjanova, A. et al. Soc. Neurosci. Abstr. 1999; 25: 1617See all References.Other evidence offered to support the claim that the BLC stores emotional memories is electrophysiological data that report the development of associative neuronal firing in the BLC when conditioned and unconditioned stimuli are paired. The interpretation of these data is based on two major assumptions: (1) increased associative neuronal firing represents memory; and (2) the BLC is the only place in the brain that exhibits such associative plasticity. The latter assumption is flawed: associative neuronal changes as a result of tone–footshock conditioning occur at all levels of the auditory system, as early as the cochlear nuclei16xLarge-scale functional connectivity in associative learning: interrelations of the rat auditory, visual, and limbic systems. Mcintosh, A. and Gonzalez-Lima, F. J. Neurophysiol. 1998; 80: 3148–3162PubMedSee all References16, in the medial geniculate17xAssociative retuning in the thalamic source of input to the amygdala and auditory cortex: receptive field plasticity in the medial division of the medial geniculate body. Edeline, J. and Weinberger, N. Behav. Neurosci. 1992; 106: 81–105Crossref | PubMed | Scopus (142)See all References17 and in the auditory cortex18xLearning-induced receptive field plasticity in the primary auditory cortex. Weinberger, N.M. Semin. Neurosci. 1997; 9: 59–67Crossref | Scopus (15)See all References18. Furthermore, the associative firing of BLC neurons decreases over minutes and parallels the extinction of behavioral responses, whereas that in the auditory cortex persists over minutes, even weeks18xLearning-induced receptive field plasticity in the primary auditory cortex. Weinberger, N.M. Semin. Neurosci. 1997; 9: 59–67Crossref | Scopus (15)See all References, 19xFear conditioning enhances different temporal components of tone-evoked spike trains in auditory cortex and lateral amygdala. Quirk, G.J. et al. Neuron. 1997; 19: 613–624Abstract | Full Text | Full Text PDF | PubMed | Scopus (351)See all References.Finally, there is at least one case of clear dissociation between LTP in the basolateral amygdala and memory. Mice that lack RasGRF, a neuron-specific nucleotide-exchange factor activated by Ca2+, lack LTP in the amygdala 30 min after an LTP-inducing theta burst stimulation that induces LTP in wild-type mice. Significantly, at the same time-point, mutant mice show normal memory for tone–footshock and context–footshock conditioning20xA role for the Ras signalling pathway in synaptic transmission and long-term memory. Brambilla, R. et al. Nature. 1997; 390: 281–286Crossref | PubMedSee all References20.Clearly, the described findings do not warrant the conclusion that emotional memories are stored in the BLC and that LTP is the mechanism that represents the stored information. The well-documented LTP of BLC neurons might be necessary for the time-limited participation of the BLC in other aspects of memory processing and storage, such as memory consolidation in various other brain regions2xIs the amygdala a locus of ‘conditioned fear’? Some questions and caveats. Cahill, L. et al. Neuron. 1999; 23: 227–228Abstract | Full Text | Full Text PDF | PubMed | Scopus (180)See all References2.