Contexts surround and imbue meaning to events; they are essential for recollecting the past, interpreting the present and anticipating the future. Indeed, the brain’s capacity to contextualize information permits enormous cognitive and behavioural flexibility. Studies of Pavlovian fear conditioning and extinction in rodents and humans suggest that a neural circuit including the hippocampus, amygdala and medial prefrontal cortex is involved in the learning and memory processes that enable context-dependent behaviour. Dysfunction in this network may be involved in several forms of psychopathology, including post-traumatic stress disorder, schizophrenia and substance abuse disorders.
Learning the relationships between aversive events and the environmental stimuli that predict such events is essential to the survival of organisms throughout the animal kingdom. Pavlovian fear conditioning is an exemplar of this form of learning that is exhibited by both rats and humans. Recent years have seen an incredible surge in interest in the neurobiology of fear conditioning. Neural circuits underlying fear conditioning have been mapped, synaptic plasticity in these circuits has been identified, and biochemical and genetic manipulations are beginning to unravel the molecular machinery responsible for the storage of fear memories. These advances represent an important step in understanding the neural substrates of a rapidly acquired and adaptive form of associative learning and memory in mammals.
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.
Electrolytic lesions of the dorsal hippocampus (DH) produce deficits in both the acquisition and expression of conditional fear to contextual stimuli in rats. To assess whether damage to DH neurons is responsible for these deficits, we performed three experiments to examine the effects of neurotoxic N-methyl-D-aspartate (NMDA) lesions of the DH on the acquisition and expression of fear conditioning. Fear conditioning consisted of the delivery of signaled or unsignaled footshocks in a novel conditioning chamber and freezing served as the measure of conditional fear. In Experiment 1, posttraining DH lesions produced severe retrograde deficits in context fear when made either 1 or 28, but not 100, days following training. Pretraining DH lesions made 1 week before training did not affect contextual fear conditioning. Tone fear was impaired by DH lesions at all training-to-lesion intervals. In Experiment 2, posttraining (1 day), but not pretraining (1 week), DH lesions produced substantial deficits in context fear using an unsignaled shock procedure. In Experiment 3, pretraining electrolytic DH lesions produced modest deficits in context fear using the same signaled and unsignaled shock procedures used in Experiments 1 and 2, respectively. Electrolytic, but not neurotoxic, lesions also increased pre-shock locomotor activity. Collectively, this pattern of results reveals that neurons in the DH are not required for the acquisition of context fear, but have a critical and time-limited role in the expression of context fear. The normal acquisition and expression of context fear in rats with neurotoxic DH lesions made before training may be mediated by conditioning to unimodal cues in the context, a process that may rely less on the hippocampal memory system.
We have shown previously that electrolytic lesions of the dorsal hippocampus (DH) produce a severe deficit in contextual fear if made 1 d, but not 28 d, after fear conditioning (Kim and Fanselow, 1992). As such, the hippocampus seems to play a time-limited role in the consolidation of contextual fear conditioning. Here, we examine retrograde amnesia of contextual fear produced by DH lesions in a within-subjects design. Unlike our previous reports, rats had both a remote and recent memory at the time of the lesion. Rats were given 10 tone-shock pairings in one context (remote memory) and 10 tone-shock pairings in a distinct context (with a different tone) 50 d later (recent memory), followed by DH or sham lesions 1 d later.Relative to controls, DH-lesioned rats exhibited no deficit in remote contextual fear, but recent contextual fear memory was severely impaired. They also did not exhibit deficits in tone freezing. This highly specific deficit in recent contextual memory demonstrated in a within-subjects design favors mnemonic over performance accounts of hippocampal involvement in fear. These findings also provide further support for a time-limited role of the hippocampus in memory storage.Key words: retrograde amnesia; hippocampus; context; fear; conditioning; freezing; rat; activity; consolidation; learning; memory After damage to the hippocampal formation, humans display anterograde amnesia of declarative memory (an inability to form new memories) that is accompanied by retrograde amnesia (RA) of declarative memory (a loss of memory acquired before the damage). In amnesics, R A is typically temporally graded; it involves the loss of memories acquired just before the lesion (recent memory), but memories acquired several years before (remote memory) remain intact [Squire and Alvarez (1995); Knowlton and Fanselow (1998); but see Nadel and Moscovitch (1997)]. This effect has been observed through use of retrospective memory tests, including those examining autobiographical details, public events, famous faces, and television shows (Rempel-C lower et al., 1996;Reed and Squire, 1998).Although many studies in animals have examined the effects of hippocampal lesions made before training (Olton et al., 1979;Morris, 1983;Phillips and LeDoux, 1992; K im et al., 1993), relatively few studies have examined temporally graded RA after damage to the hippocampal formation (Winocur, 1990; ZolaMorgan and Squire, 1990;Cho et al., 1993;Bolhuis et al., 1994;Kim et al., 1995;Cho and Kesner, 1996;Wiig et al., 1996;Nadel and Moscovitch, 1997). K im and Fanselow (1992) gave animals Pavlovian fear conditioning in which a tone conditional stimulus (CS) was paired with a shock unconditional stimulus (US) several times in a novel context. Rats trained in this manner develop a fear of both the tone and the training context, which can be measured as freezing, an adaptive species-specific defense reaction (Bolles, 1970;Fanselow, 1980). Electrolytic lesions of the dorsal hippocampus (DH) made 1 d, but not 28 d, after training abolished conte...
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