Amygdala-lesioned Animals Research Articles

Early amygdala or hippocampus damage influences adolescent female social behavior during group formation.

This study continues a longitudinal analysis of rhesus macaque social behavior following bilateral neonatal ibotenic acid lesions of the amygdala or hippocampus, or sham operations. The social behavior of female subjects was evaluated at a critical developmental time point-the transition to adulthood. At approximately 4 years of age, female subjects were housed in small groups with other female subjects and reproductively viable adult males. As compared with neurologically intact control animals and animals with early amygdala damage, animals with early hippocampal damage were more social with their female peers. In contrast, as compared with control animals, animals with early amygdala damage spent less time with the males, engaged less frequently in behaviors typical of reproductive consortships, had higher frequencies of self-directed stereotypies, and became pregnant later. Males also generated fewer communicative signals toward animals with early amygdala damage than to control animals and animals with early hippocampus damage. Rates of sexual behavior were generally low for all animals, and there were no lesion-based differences in their frequencies. Discriminant function analyses demonstrated that patterns of affiliative social behaviors differed across the 3 experimental groups, both in terms of the social behaviors directed to the males, and the social behaviors generated by the males toward the females. In 4 of the 5 social groups, amygdala-lesioned animals were lowest ranked, potentially contributing to reduced sociability interactions with males. Other potential mechanisms and the experiments needed to elucidate them are discussed. (PsycINFO Database Record

The effects of neonatal amygdala or hippocampus lesions on adult social behavior

The present report details the final phase of a longitudinal evaluation of the social behavior in a cohort of adult rhesus monkeys that received bilateral neurotoxic lesions of the amygdala or hippocampus, or sham operations at 2 weeks of age. Results were compared to previous studies in which adult animals received amygdala lesions and were tested in a similar fashion. Social testing with four novel interaction partners occurred when the animals were between 7 and 8 years of age. Experimental animals interacted with two male and two female partners in two conditions – one in which physical access was restricted (the constrained social access condition) and a second in which physical access was unrestricted (the unconstrained social access condition). Across conditions and interaction partners, there were no significant effects of lesion condition on the frequency or duration of social interactions. As a group, the hippocampus-lesioned animals generated the greatest number of communicative signals during the constrained social access condition. Amygdala-lesioned animals generated more frequent stress-related behaviors and were less exploratory. Amygdala and hippocampus-lesioned animals demonstrated greater numbers of stereotypies than control animals. Subtle, lesion-based differences in the sequencing of behaviors were observed. These findings suggest that alterations of adult social behavior are much less prominent when damage to the amygdala occurs early in life rather than in adulthood.

Basolateral amygdala lesions abolish mutual reward preferences in rats

In a recent study, we demonstrated that rats prefer mutual rewards in a Prosocial Choice Task. Here, employing the same task, we show that the integrity of basolateral amygdala was necessary for the expression of mutual reward preferences. Actor rats received bilateral excitotoxic (n=12) or sham lesions (n=10) targeting the basolateral amygdala and were subsequently tested in a Prosocial Choice Task where they could decide between rewarding (“Both Reward”) or not rewarding a partner rat (“Own Reward”), either choice yielding identical reward to the actors themselves. To manipulate the social context and control for secondary reinforcement sources, actor rats were paired with either a partner rat (partner condition) or with an inanimate rat toy (toy condition). Sham-operated animals revealed a significant preference for the Both-Reward-option in the partner condition, but not in the toy condition. Amygdala-lesioned animals exhibited significantly lower Both-Reward preferences than the sham group in the partner but not in the toy condition, suggesting that basolateral amygdala was required for the expression of mutual reward preferences. Critically, in a reward magnitude discrimination task in the same experimental setup, both sham-operated and amygdala-lesioned animals preferred large over small rewards, suggesting that amygdala lesion effects were restricted to decision making in social contexts, leaving self-oriented behavior unaffected.

Adult social behavior with familiar partners following neonatal amygdala or hippocampus damage.

The social behavior in a cohort of adult animals who received ibotenic acid lesions of the amygdala (4 female, 3 male) or hippocampus (5 female, 3 male) as neonates, and sham-operated controls (4 female, 4 male) was evaluated in their home environments with the familiar opposite sex monkey (pair-mate) with whom they were housed. Amygdala-lesioned animals spent less time with their familiar partners and engaged in higher frequencies of stress-related behaviors than control animals. Hippocampus-lesioned animals spent significantly more time socially engaging their pair-mates than both control and amygdala-lesioned animals. These results suggest that early damage to the amygdala or hippocampus subtly alter patterns of adult social behavior in a familiar context and stand in sharp contrast to extant studies of early damage to the amygdala or hippocampus and to the more dramatically altered patterns of behavior observed after damage to the adult amygdala.

The Impact of Early Amygdala Damage on Juvenile Rhesus Macaque Social Behavior

The present experiments continue a longitudinal study of rhesus macaque social behavior following bilateral neonatal ibotenic acid lesions of the amygdala or hippocampus, or sham operations. Juvenile animals (approximately 1.5-2.5 years) were tested in four different social contexts--alone, while interacting with one familiar peer, while interacting with one unfamiliar peer, and in their permanent social groups. During infancy, the amygdala-lesioned animals displayed more interest in conspecifics (indexed by increased affiliative signaling) and paradoxically demonstrated more submission or fear (Bauman, Lavenex, Mason, Capitanio, & Amaral, 2004a, this journal). When these animals were assessed as juveniles, differences were less striking. Amygdala-lesioned animals generated fewer aggressive and affiliative signals (e.g., vocalizations, facial displays) and spent less time in social interactions with familiar peers. When animals were observed alone or with an unfamiliar peer, amygdala-lesioned animals, compared with other subjects, spent more time being inactive and physically explored the environment less. Despite the subtle, lesion-based differences in the frequency and duration of specific social behaviors, there were lesion-based differences in the organization of behavior such that lesion groups could be identified based on the patterning of social behaviors in a discriminant function analysis. The findings indicate that, although overall frequencies of many of the observed behaviors do not differ between groups, the general patterning of social behavior may distinguish the amygdala-lesioned animals.

Contribution of the amygdala, but not orbitofrontal or medial prefrontal cortices, to the expression of flavour preferences in marmoset monkeys

The development of food preferences contributes to a balanced diet, and involves both innate and learnt factors. By associating flavour cues with the reinforcing properties of the food (i.e. postingestive nutrient cues and innately preferred tastes, such as sweetness), animals acquire individual preferences. How the brain codes and guides selection when the subject has to choose between different palatable foods is little understood. To investigate this issue, we trained common marmoset monkeys (Callithrix jacchus) to respond to abstract visual patterns on a touch-sensitive computer screen to gain access to four different flavoured juices. After preferences were stable, animals received excitotoxic lesions of either the amygdala, the orbitofrontal cortex or the medial prefrontal cortex. Neither the orbitofrontal nor the medial prefrontal cortex lesions affected pre-surgery-expressed flavour preferences or the expression of preferences for novel flavours post-surgery. In contrast, amygdala lesions caused a shift in the preferences for juices expressed pre-surgery such that, post-surgery, juices were chosen according to their overall carbohydrate (simple sugars) content or 'sweetness'. Subsequent tests revealed that amygdala-lesioned animals only expressed juice preferences if they differed in 'sweetness'. Unlike controls, orbitofrontal cortex-lesioned and medial prefrontal cortex-lesioned animals, they were unable to display preferences between juices matched for 'sweetness' i.e. 5% sucrose solutions aromatised with different essential oils. The most parsimonious explanation is that the amygdala contributes to the expression of food preferences based on learnt cues but not those based on an innate preference for sweetness.

Neonatal amygdala lesions alter responsiveness to objects in juvenile macaques

The amygdala is widely recognized to play a central role in emotional processing. In nonhuman primates, the amygdala appears to be critical for generating appropriate behavioral responses in emotionally salient contexts. One common finding is that macaque monkeys that receive amygdala lesions as adults are behaviorally uninhibited in the presence of potentially dangerous objects. While control animals avoid these objects, amygdala-lesioned animals readily interact with them. Despite a large literature documenting the role of the amygdala in emotional processing in adult rhesus macaques, little research has assessed the role of the amygdala across the macaque neurodevelopmental trajectory. We assessed the behavioral responses of 3-year-old (juvenile) rhesus macaques that received bilateral ibotenic acid lesions of the amygdala or hippocampus at 2 weeks of age. Animals were presented with salient objects known to produce robust fear-related responses in macaques (e.g., snakes and reptile-like objects), mammal-like objects that included animal-like features (e.g., eyes and mouths) but not reptile-like features (e.g., scales), and non-animal objects. The visual complexity of objects was scaled to vary the objects' salience. In contrast to control and hippocampus-lesioned animals, amygdala-lesioned animals were uninhibited in the presence of potentially dangerous objects. They readily retrieved food rewards placed near these objects and physically explored the objects. Furthermore, while control and hippocampus-lesioned animals differentiated between levels of object complexity, amygdala-lesioned animals did not. Taken together, these findings suggest that early damage to the amygdala, like damage sustained during adulthood, permanently compromises emotional processing.

Neonatal amygdala or hippocampus lesions influence responsiveness to objects.

Medial temporal lobe brain structures, such as the amygdala, play an important role in the normal perception and generation of emotional behavior. Little research, however, has assessed the role of such structures across the neurodevelopmental trajectory. We assessed emotional behavioral responses of rhesus macaques that received bilateral ibotenic acid lesions of the amygdala or hippocampus at 2 weeks of age and sham-operated controls. At 9 and 18 months of age, animals interacted with novel objects that varied in visual complexity as a means of varying emotional salience. All animals behaved differently in the presence of visually simple, as compared to complex, objects, suggesting that they were sensitive to variation in emotional salience. Across both experiments, amygdala-lesioned animals appeared to be less behaviorally inhibited insofar as they explored all objects most readily. Interestingly, hippocampus-lesioned animals' propensity for exploration mirrored that of control animals in some contexts but that of amygdala-lesioned animals in other contexts. At 18 months of age, both amygdala-lesioned and hippocampus-lesioned animals were judged to be less fearful than controls during the testing procedure. Implications for understanding the neurobiology of emotional behavior are discussed.

Effects of neonatal amygdala or hippocampus lesions on resting brain metabolism in the macaque monkey: A microPET imaging study

Longitudinal analysis of animals with neonatal brain lesions enables the evaluation of behavioral changes during multiple stages of development. Interpretation of such changes, however, carries the caveat that permanent neural injury also yields morphological and neurochemical reorganization elsewhere in the brain that may lead either to functional compensation or to exacerbation of behavioral alterations. We have measured the long-term effects of selective neonatal brain damage on resting cerebral glucose metabolism in nonhuman primates. Sixteen rhesus monkeys ( Macaca mulatta) received neurotoxic lesions of either the amygdala ( n = 8) or hippocampus ( n = 8) when they were two weeks old. Four years later, these animals, along with age- and experience-matched sham-operated control animals ( n = 8), were studied with high-resolution positron emission tomography (microPET) and 2-deoxy-2[ 18F]fluoro- d-glucose ([ 18F]FDG) to detect areas of altered metabolism. The groups were compared using an anatomically-based region of interest analysis. Relative to controls, amygdala-lesioned animals displayed hypometabolism in three frontal lobe regions, as well as in the neostriatum and hippocampus. Hypermetabolism was also evident in the cerebellum of amygdala-lesioned animals. Hippocampal-lesioned animals only showed hypometabolism in the retrosplenial cortex. These results indicate that neonatal amygdala and hippocampus lesions induce very different patterns of long-lasting metabolic changes in distant brain regions. These observations raise the possibility that behavioral alterations in animals with neonatal lesions may be due to the intended damage, to consequent brain reorganization or to a combination of both factors.

The Role of the Primate Amygdala in Conditioned Reinforcement

Conditioned reinforcement refers to the capacity of a conditioned stimulus to support instrumental behavior by acquiring affective properties of the primary reinforcer with which it is associated. Conditioned reinforcers maintain behavior over protracted periods of time in the absence of, and potentially in conflict with, primary reinforcers and as such may play a fundamental role in complex social behavior. A relatively large body of evidence supports the view that the amygdala (and in particular the basolateral area) contributes to conditioned reinforcement by maintaining a representation of the affective value of conditioned stimuli. However, a recent study in primates (Malkova et al., 1997), using a second-order visual discrimination task, suggests that the amygdala is not critical for the conditioned reinforcement process. In the present study, excitotoxic lesions of the amygdala in a new world primate, the common marmoset, resulted in a progressive impairment in responding under a second-order schedule of food reinforcement. In addition, the responding of amygdala-lesioned animals was insensitive to the omission of the conditioned reinforcer, unlike that of control animals, for which responding was markedly reduced. In contrast, lesioned animals were unimpaired when responding on a progression of fixed-ratio schedules of primary reinforcement. These data confirm that the amygdala is critical for the conditioned reinforcement process in primates, and taken together with other recent work in monkeys, these results suggest that the contribution of the amygdala is to provide the affective value of specific reinforcers as accessed by associated conditioned stimuli.

Role of the Hippocampus, the Bed Nucleus of the Stria Terminalis, and the Amygdala in the Excitatory Effect of Corticotropin-Releasing Hormone on the Acoustic Startle Reflex

Previously, we demonstrated that transection of the fimbria/fornix blocked the excitatory effect of corticotropin-releasing hormone (CRH) on startle (CRH-enhanced startle), suggesting that the hippocampus and its efferent target areas that communicate via the fimbria may be critically involved in CRH-enhanced startle. The bed nucleus of the stria terminalis (BNST) receives direct projections from the ventral hippocampus via the fimbria/fornix. Therefore, the role of the ventral hippocampus, the BNST, and the amygdala in CRH-enhanced startle was investigated. NMDA lesions of the BNST completely blocked CRH-enhanced startle, whereas chemical lesions of the ventral hippocampus and the amygdala failed to block CRH-enhanced startle. However, the same amygdala-lesioned animals showed a complete blockade of fear-potentiated startle, a conditioned fear response sensitive to manipulations of the amygdala. In contrast, BNST-lesioned rats had normal fear-potentiated startle. This indicates a double dissociation between the BNST and the amygdala in two different paradigms that enhance startle amplitude. Microinfusions of CRH into the BNST, but not into the ventral hippocampus, mimicked intracerebroventricular CRH effects. Furthermore, infusion of a CRH antagonist into the BNST blocked CRH-enhanced startle in a dose-dependent manner. Control studies showed that this blockade did not result from either leakage of the antagonist into the ventricular system or a local anesthetic effect caused by infusion of the antagonist into the BNST. The present studies strongly suggest that CRH in the CSF can activate the BNST, which could lead to activation of brainstem and hypothalamic BNST target areas involved in anxiety and stress responses.

Changes in male copulatory behavior after sexual exciting stimuli: Effects of medial amygdala lesions

A paradigm was developed to investigate how precoital sexual arousal affects parameters of sexual behavior in male rats. Estrous females in a wire mesh cage were used to induce sexual arousal before the sexual interaction test. In control procedures, males were presented in a wire mesh cage or else there was no stimuli at all. The results indicate that ejaculation latency is consistently reduced after preexposure to a female, but not after preexposure to a male, showing that the effect is specific for precoital sexual arousal. Other parameters were affected by precoital sexual arousal in some, but not in all experiments. Reductions in intromission latency moreover, were observed after both preexposure to a male and preexposure to a female, indicating that general social excitement affects this parameter. Preexposure to females for 10 minutes or 3 hours produced similar results. It was subsequently found that medial amygdala-lesioned (AME) animals differed from sham-lesioned (SHAM) controls with respect to their reaction to precoital sexual arousal. The results show that AME-lesioned animals, in contrast to SHAM-animals, do not show reduced ejaculation latencies after preexposure to an estrous female. The results are in line with the idea that AME-lesioned animals are deficient in the assimilation of information on sexual exciting stimuli.

Fetal brain transplants induce recuperation of taste aversion learning

Rats showing disrupted taste aversion due to gustatory neocortex or amygdala lesions were transplanted into the lesioned area with homologous brain tissue obtained from 17-day-old fetuses. Comparisons of taste aversions scores before and after the graft, revealed that the grafted animals significantly recuperated taste aversions, whereaa cortical lesioned animals without grafts did not. Surprisingly, however, amygdala-lesioned animals without graft presented spontaneous recovery. These results not only support the hypothesis that fetal brain transplants can restore cognitive functions, but also that there are some fundamental functional differences between the gustatory neocortex and the amygdala in the regulation of the processes involved in the acquisition and retention of taste aversion.

Effect of Lidocaine Pretreatment on Cocaine-Induced Behavior in Normal and Amygdala-Lesioned Rats

Animals treated with daily lidocaine (60 mg/kg, i.p.) develop progressive increases in pathological eating of nonnutritive substances, i.e. omniphagia. Bilateral amygdala lesions blocked the development of lidocaine-induced omniphagia. Following 32 daily injections of lidocaine, both lesioned and nonlesioned animals showed greater cocaine-induced hyperactivity than saline-pretreated controls. These data suggest cross-sensitization between the two local anesthetics lidocaine and cocaine, even though lidocaine does not possess the psychomotor stimulant effects of cocaine. Amygdala-lesioned animals showed greater cocaine-induced vertical rearing activity compared to controls. The lesion data suggest that the amygdala is differentially involved in the progressive behavioral sensitization to both chronic lidocaine and cocaine.

The effect of training technique and amygdala lesions on the acquisition and retention of a taste aversion

This study explored the effect of amygdala lesions in rats on the acquisition of a taste aversion using either a single bottle or two bottle training procedure. The results indicated that training procedure was an important factor in the development of a taste aversion. Animals with amygdala lesions acquired an aversion as rapidly as control animals using a two bottle technique, but showed a marked retardation in learning when a single bottle technique was employed. In extinction, all amygdala-lesioned animals showed a persistent aversion to the taste. These results were taken to support the concept that lesions to the amygdala produce an inhibitory deficit.

Amygdala lesions: Differential effects on activity and reactivity to light of rats

The activity of amygdala-lesioned rats was compared with that of normal controls and amygdala shams under shuttlebox conditions of total darkness and single-compartment illumination. Although the activity (movement between compartments) of the groups did not differ under either of these conditions, the single-compartment illumination significantly decreased the activity of all three groups. A further analysis of the percentage of test time spent in the illuminated compartment indicated that the amygdala-lesioned animals spent significantly less time there than did the other two groups. The differential effects of the lesions on activity and reactivity to light were discussed in terms of changes in general responsiveness following amygdala damage.