Neuronal signalling of fear memory.

Department of Psychology and Neuroscience Program, University of Michigan, Ann Arbor, Michigan 48109, USA.
Nature reviews. Neuroscience (Impact Factor: 31.38). 12/2004; 5(11):844-52. DOI: 10.1038/nrn1535
Source: PubMed

ABSTRACT The learning and remembering of fearful events depends on the integrity of the amygdala, but how are fear memories represented in the activity of amygdala neurons? Here, we review recent electrophysiological studies indicating that neurons in the lateral amygdala encode aversive memories during the acquisition and extinction of Pavlovian fear conditioning. Studies that combine unit recording with brain lesions and pharmacological inactivation provide evidence that the lateral amygdala is a crucial locus of fear memory. Extinction of fear memory reduces associative plasticity in the lateral amygdala and involves the hippocampus and prefrontal cortex. Understanding the signalling of aversive memory by amygdala neurons opens new avenues for research into the neural systems that support fear behaviour.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Studies on male Sprague–Dawley rats using vital intracranial microdialysis and high-performance liquid chromatography showed that exploratory behavior in a novel context was accompanied by increases in extracellular citrulline (a co-product of NO synthesis) in the medial part of the nucleus accumbens, and these were blocked by local administration of the neuronal NO synthase inhibitor 7-nitroindazole (0.5 mM). Presentation during exploratory activity of a tone which had previously been combined with electrocutaneous stimulation decreased exploratory behavior and, secondly, inhibited the increase in the nucleus accumbens citrulline level induced by exploratory behavior. These effects were not seen in control animals in which the tone had not been associated with electrocutaneous stimulation. These data provide the first evidence for the involvement of the medial part of the nucleus accumbens in transferring the effects of fear to exploratory behavior and demonstrate that inhibition of nitrergic transmission may make a contribution to this process.
    Neuroscience and Behavioral Physiology 11/2013; 43(9):1076-1083. DOI:10.1007/s11055-013-9852-7
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Anxiety, trauma and stress-related disorders are often characterized by a loss of context-appropriate emotional responding. The contextual retrieval of emotional memory involves hippocampal projections to the medial prefrontal cortex and amygdala; however the relative contribution of these projections is unclear. To address this question, we characterized retrieval-induced Fos expression in ventral hippocampal (VH) neurons projecting to the prelimbic cortex (PL) and basal amygdala (BA) after the extinction of conditioned fear in rats. After extinction, freezing behavior (an index of learned fear) to the auditory conditioned stimulus was suppressed in the extinction context, but was "renewed" in another context. Hippocampal neurons projecting to either PL or BA exhibited similar degrees of context-dependent Fos expression; there were more Fos-positive neurons in each area after the renewal, as opposed, to suppression of fear. Importantly, however, VH neurons projecting to both PL and BA were more likely to express Fos during fear renewal than neurons projecting to either PL or BA alone. These data suggest that although projections from the hippocampus to PL and BA are similarly involved in the contextual retrieval of emotional memories, VH neurons with collaterals to both areas may be particularly important for synchronizing prefrontal-amygdala circuits during fear renewal.
    Scientific Reports 02/2015; 5:8388. DOI:10.1038/srep08388 · 5.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A long-standing hypothesis termed "Hebbian plasticity" suggests that memories are formed through strengthening of synaptic connections between neurons with correlated activity. In contrast, other theories propose that coactivation of Hebbian and neuromodulatory processes produce the synaptic strengthening that underlies memory formation. Using optogenetics we directly tested whether Hebbian plasticity alone is both necessary and sufficient to produce physiological changes mediating actual memory formation in behaving animals. Our previous work with this method suggested that Hebbian mechanisms are sufficient to produce aversive associative learning under artificial conditions involving strong, iterative training. Here we systematically tested whether Hebbian mechanisms are necessary and sufficient to produce associative learning under more moderate training conditions that are similar to those that occur in daily life. We measured neural plasticity in the lateral amygdala, a brain region important for associative memory storage about danger. Our findings provide evidence that Hebbian mechanisms are necessary to produce neural plasticity in the lateral amygdala and behavioral memory formation. However, under these conditions Hebbian mechanisms alone were not sufficient to produce these physiological and behavioral effects unless neuromodulatory systems were coactivated. These results provide insight into how aversive experiences trigger memories and suggest that combined Hebbian and neuromodulatory processes interact to engage associative aversive learning.

Full-text (2 Sources)

Available from
May 15, 2014