Plasticity in the CNS is essential for the representation of new information, and an important challenge is to understand how various forms of experience-dependent plasticity are reflected in the activity of neuronal populations that support behaviour. This article reviews recent single-unit recording studies that have provided considerable insight into the neuronal mechanisms of learning and memory, focusing particularly on Pavlovian fear conditioning.
The search for the neurophysiological mechanism of aversive memory began in the early 1960s with the observation that an auditory stimulus that was paired with an electric shock modified auditory-evoked field potentials in cats and rats. Subsequent single-unit recording studies in cats and monkeys showed conditioning-induced changes in evoked spike activity in several brain areas, including the midbrain, thalamus and cortex.
An influential study by Kapp and co-workers provided evidence that the central nucleus of the amygdala is required for Pavlovian fear conditioning. Subsequent single-unit recording studies of this nucleus revealed associative plasticity, indicating that the amygdala might be a site of plasticity in fear conditioning.
The lateral nucleus of the amygdala (LA) receives direct projections from the medial subdivision of the medial geniculate nucleus and the adjacent thalamic posterior intralaminar nucleus (MGm/PIN), and it relays this information by way of the basal amygdaloid nuclei to the central nucleus. Small lesions of the LA or the MGm/PIN prevent fear conditioning, whereas large lesions of the auditory cortex or striatum do not.
The expression of fear is neither sufficient nor necessary for the expression of associative plasticity in the LA, supporting the view that LA neurons encode fear memories. The essence of this mnemonic code seems to be contained in the rate at which LA neurons fire action potentials in response to auditory conditional stimuli, although the LA might also signal fear associations by the timing of spikes within a conditional stimulus-evoked spike train.
The amygdala also seems to have a vital role in the extinction of learned fear, an inhibitory learning process that has important clinical relevance as a treatment for anxiety disorders. The mediation of extinction by the amygdala is manifested in the firing of LA neurons.
This research opens up new avenues to investigate how the hippocampus, prefrontal cortex and amygdala interact during the acquisition, storage and retrieval of fear memories, and the cellular and synaptic mechanisms that encode inhibitory extinction memories together with excitatory fear memories.
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.
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The authors thank K. Goosens and two anonymous reviewers for helpful comments on the manuscript. This work was supported by grants from the National Institute of Mental Health.
The authors declare no competing financial interests.
An extracellular electrode that comprises four juxtaposed recording channels, which can be used to disambiguate the signals emitted by individual point sources. Because each neuron occupies a unique position in space, its spikes are 'seen' slightly differently by each electrode, providing a unique signature. This technique allows the identification of many more neurons than there are sampling electrodes.
- LONG-TERM POTENTIATION
(LTP) An enduring increase in the amplitude of excitatory postsynaptic potentials as a result of high-frequency (tetanic) stimulation of afferent pathways. It is measured both as the amplitude of excitatory postsynaptic potentials and as the magnitude of the postsynaptic cell-population spike. LTP is most frequently studied in the hippocampus and is often considered to be the cellular basis of learning and memory in vertebrates.
- BASOLATERAL AMYGDALA
The region of the amygdala that encompasses the lateral, basolateral and basomedial nuclei.
- INSTRUMENTAL AVOIDANCE LEARNING
Instrumental learning is a form of learning that takes place through reinforcement (or punishment) that is contingent on the performance (or withholding) of a particular behaviour. So, the subject's response is instrumental in producing an outcome. Compare with Pavlovian learning.
The reduction in the conditioned response after non-reinforced presentations of the conditional stimulus.
- RECEPTIVE FIELD
That limited domain of the sensory environment to which a given sensory neuron is responsive, such as a limited frequency band in audition or a limited area of space in vision.
- CONDITIONED LEVER-PRESS SUPPRESSION
The reduction in pressing for food reward in the presence of a fear-conditioned stimulus.
- THETA OSCILLATIONS
Rhythmic neural activity with a frequency of 4–8 Hz.
- PREFRONTAL CORTEX
(PFC) The non-motor sectors of the frontal lobe that receive input from the dorsomedial thalamic nucleus and subserve working memory, complex attentional processes and executive functions such as planning, behavioural inhibition, logical reasoning, action monitoring and social cognition.
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Maren, S., Quirk, G. Neuronal signalling of fear memory. Nat Rev Neurosci 5, 844–852 (2004). https://doi.org/10.1038/nrn1535
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