The nonhuman primate amygdala is necessary for the acquisition but not the retention of fear-potentiated startle.

BACKGROUND: In a previous study, we found that rhesus monkeys prepared with bilateral lesions of the amygdala failed to acquire fear-potentiated startle to a visual cue. However, a second group of monkeys, which received the lesion after training, successfully demonstrated fear-potentiated startle learned prior to the lesion. METHODS: In the current experiment, the eight monkeys used in the second part of the original study, four of which had bilateral amygdala lesions and the four control animals, were trained using an auditory cue and tested in the fear-potentiated startle paradigm. This test was performed to determine whether they could acquire fear-potentiated startle to a new cue. RESULTS: Monkeys with essentially complete damage to the amygdala (based on histological analysis) that had retained and expressed fear-potentiated startle to a visual cue learned before the lesion failed to acquire fear-potentiated startle to an auditory cue when training occurred after the lesion. CONCLUSIONS: The results suggest that while the nonhuman primate amygdala is essential for the initial acquisition of fear conditioning, it does not appear to be necessary for the memory and expression of conditioned fear. These findings are discussed in relation to a network of connections between the amygdala and the orbitofrontal cortex that may subserve different component processes of fear conditioning.

Acoustic startle reflex in rhesus monkeys: a review.

Modulation of the acoustic startle response is a simple and objective indicator of emotionality and attention in rodents and humans. This finding has proven extremely valuable for the analysis of neural systems associated with fear and anxiety. Until recently, there have been few efforts to develop acoustic startle measurement in non-human primates. Here we review recent work in which whole body acoustic startle amplitude has been measured in rhesus monkeys. Initial studies revealed that the amplitude of whole body startle in monkeys, as in rodents and humans, is directly proportional to acoustic stimulus intensity and gradually habituates with repeated exposures. Presentation of a weak acoustic stimulus 25-5,000 msec before a startle stimulus reduces startle amplitude by 40-50% depending on inter-stimulus interval length (prepulse inhibition). We have also measured significant fear-potentiated startle in the presence of a visual stimulus after pairing it with an inescapable pulse of pressurized air (fear-potentiated startle). This effect was reduced by diazepam and morphine, but not by buspirone. Ibotenic acid-induced lesions of the amygdala prevented the acquisition of fear-potentiated startle but, remarkably, did not prevent the expression of fear-potentiated startle when fear conditioning was carried out prior to the lesion. Finally, we have developed an objective measure of fear inhibition in monkeys using a novel conditioned inhibition procedure identical to one used in rats and humans. Our data demonstrate that acoustic startle in non-human primates successfully bridges rodent and human research. The opportunity now emerges to link concepts developed in rodents to the more complex neuroanatomical and cognitive processes common to monkeys and humans.

Role of the primate amygdala in fear-potentiated startle: effects of chronic lesions in the rhesus monkey.

In experiment 1, we assessed the role of the primate amygdala and hippocampus in the acquisition of learned fear measured with fear-potentiated startle. Three groups of six rhesus monkeys were prepared with bilateral ibotenic acid lesions of the amygdaloid complex and the hippocampus or were sham operated. Selective ibotenic acid lesions of the amygdala, but not the hippocampus, blocked the acquisition of fear-potentiated startle. In experiment 2, we assessed the role of the primate amygdala in the expression of fear-potentiated startle. Surprisingly, animals that sustained amygdala damage after they successfully learned fear-potentiated startle expressed normal fear-potentiated startle, despite a complete amygdala lesion based on magnetic resonance imaging assessments. These results suggest that although the amygdala is necessary for the initial acquisition of fear-potentiated startle, it is not necessary for the retention and expression of fear-potentiated startle. These findings are discussed in relation to the role of the amygdala in emotional learning and in cross-species comparisons of emotional behavior.

Fornix, medial prefrontal cortex, nucleus accumbens, and mediodorsal thalamic nucleus: roles in a fear-based context discrimination task.

The goal of the present study was to evaluate the contributions of various brain structures anatomically and functionally linked to the hippocampus and amygdala in a fear-based context discrimination task. The brain areas of interest included the fornix, medial prefrontal cortex, mediodorsal (MD) thalamic nucleus, and nucleus accumbens. Damage to the MD thalamic nucleus and medial prefrontal cortex produced the largest impairment in context-specific fear responses. Damage to the fornix impaired some fear responses (freezing, ultrasonic vocalizations, defecation, and approach/avoidance) while leaving conditioned fear expression of heart rate and urination unaltered. Damage to the nucleus accumbens was also coupled with deficits in the discriminative expression of some (heart rate, urination, and ultrasonic vocalizations) but sparing of context-appropriate freezing, defecation, and approach/avoidance behaviors.

The significance of circadian phase for performance on a reward-based learning task in hamsters.

In humans and animal models, circadian modulation of learning has been demonstrated on numerous tests. However, it is unclear which aspects of the cognitive process are rhythmically regulated. In these experiments, we used a conditioned place preference task in hamsters to ask whether memory acquisition (hypothesis 1) or memory recall and performance (hypothesis 2) were subject to circadian modulation. In golden hamsters, access to a running wheel has been used as a reward to condition a place preference, but when given unrestricted access to a wheel, animals perform most of their spontaneous running within a few hours each day or circadian cycle. This suggested that either the perceived reward value of the wheel changes through the day or that the response to this reward is temporally restricted. Contrary to the hypotheses, we found that learning was not tied to the time of training nor to the time of testing, but rather animals showed a preference for a reward-paired context only at the circadian time that training had taken place. Timing is not an explicit discriminative cue in these experiments. Hence, the learning mechanism must be predisposed to register circadian time as an attribute during context learning.