Basolateral Amygdala Lesions Research Articles

Basolateral amygdala lesions block glucocorticoid-induced modulation of memory for spatial learning.

Basolateral amygdala lesions block glucocorticoid-induced modulation of memory for spatial learning.

Neurotoxic Lesions of Basolateral, But Not Central, Amygdala Interfere with Pavlovian Second-Order Conditioning and Reinforcer Devaluation Effects

Considerable evidence suggests that various discrete nuclei within the amygdala complex are critically involved in the assignment of emotional significance or value to events through associative learning. Much of this evidence comes from aversive conditioning procedures. For example, lesions of either basolateral amygdala (ABL) or the central nucleus (CN) interfere with the acquisition or expression of conditioned fear. The present study examined the effects of selective neurotoxic lesions of either ABL or CN on the acquisition of positive incentive value by a conditioned stimulus (CS) with two appetitive Pavlovian conditioning procedures. In second-order conditioning experiments, rats first received light-food pairings intended to endow the light with reinforcing power. The acquired reinforcing power of the light was then measured by examining its ability to serve as a reinforcer for second-order conditioning of a tone when tone-light pairings were given in the absence of food. Acquisition of second-order conditioning was impaired in rats with ABL lesions but not in rats with CN lesions. In reinforcer devaluation procedures, conditioned responding of rats with ABL lesions was insensitive to postconditioning changes in the value of the reinforcer, whereas rats with CN lesions, like normal rats, were able to spontaneously adjust their CRs to the current value of the reinforcer. The results of both test procedures indicate that ABL, but not CN, is part of a system involved in CSs' acquisition of positive incentive value. Together with evidence that identifies a role for CN in certain changes in attentional processing of CSs in conditioning, these results suggest that separate amygdala subsystems contribute to a variety of processes inherent in associative learning.

Lack of a temporal gradient of retrograde amnesia following NMDA-induced lesions of the basolateral anygdala assessed with the fear-potentiated startle paradigm.

M. Kim and M. Davis (1993b) previously reported that electrolytic lesions of the central nucleus of the amygdala, made 6 or 30 days after training, completely blocked the expression of fear-potentiated startle in rats. The present study shows that excitotoxic lesions of the basolateral amygdala also block fear-potentiated startle and do so whether the lesions are made soon (i.e., 6 days) or long (i.e., 30 days) after training. The relevance of these findings to various theories of amygdala function is discussed.

Effects of lesions to amygdala, ventral subiculum, medial prefrontal cortex, and nucleus accumbens on the reaction to novelty: implication for limbic-striatal interactions.

The effects of bilateral excitotoxic lesions of 3 major sources of afferents to the ventral striatum (nucleus accumbens) were compared on an open field test of food neophobia allowing the choice between familiar and novel food. Whereas lesions of the basolateral amygdala and ventral subiculum had qualitatively similar effects to reduce food neophobia (although not affecting the latency to eat), amygdala lesions increased and the ventral subiculum decreased locomotor activity. In contrast, damage to the ventromedial prelimbic prefrontal cortex only affected initial food choice and latency measures. By comparison, excitotoxic lesions of the nucleus accumbens itself and intra-accumbens infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist AP5 increased activity and attenuated food neophobia. Results are discussed in terms of the role of limbic and prefrontal neuronal networks converging in the nucleus accumbens to control different aspects of the behavioral response to novelty.

Basolateral amygdala lesions block glucocorticoid-induced modulation of memory for spatial learning.

This study examined the role of the amygdala in mediating the effects of glucocorticoids on spatial memory in rats. Adrenalectomy (ADX) induced 4-5 days prior to training impaired memory in a water-maze spatial task. This effect was reversed by a posttraining injection of dexamethasone (0.3 mg/kg sc) but not by corticosterone (0.3 mg/kg). Lesions of the basolateral (BLA), but not the central (CEA) or the medial (MEA), amygdala blocked the effects of ADX and dexamethasone. ADX also impaired acquisition. CEA, MEA, and BLA lesions blocked the ADX effect on acquisition. In adrenally intact rats, intracerebroventricular posttraining injections of a specific glucocorticoid receptor (GR or Type-II) antagonist impaired retention, and BLA lesions blocked the effect of the GR antagonist. These findings provide evidence that the BLA is involved in mediating glucocorticoid influences on learning and memory.

Basolateral amygdala lesions do not disrupt latent inhibition

Latent inhibition (LI) is a measure of retarded conditioning to a previously presented non-reinforced stimulus that is impaired in schizophrenic patients and in rats treated with amphetamine, and is restored in both by neuroleptic drugs. In terms of neural substrates, LI depends on the integrity of the nucleus accumbens (NAC) and the inputs to this structure from the hippocampal formation and adjacent cortical areas. The present experiments investigated the effects of electrolytic lesions to the basolateral amygdala (BLA), which is another major source of input to the NAC, on the LI effect. LI was assessed in a conditioned emotional response (CER) procedure in rats licking for water, consisting of three stages: pre-exposure, in which the to-be-conditioned stimulus (a tone) was repeatedly presented without being followed by reinforcement; conditioning, in which the pre-exposed stimulus was paired with reinforcement (a foot shock); and test, in which LI was indexed by the animal's degree of suppression of licking during tone presentation. In Expt. 1, which used a lesion at a more posterior location, no effect on either LI or CER conditioning was seen. In Expt. 2, lesion at a more anterior location reduced the magnitude of CER conditioning in both the pre-exposed and the non-pre-exposed animals, but left the LI effect intact. The latter lesion did not affect spontaneous and amphetamine-induced activity (Expt. 3). These results suggest that the development of LI is not dependent on the amygdalar input to the NAC, but that the input from the anterior aspects of BLA to the NAC is involved in the establishment of stimulus-reinforcement associations.

Synaptic plasticity in the basolateral amygdala induced by hippocampal formation stimulation in vivo

Several studies suggest that axonal projections from the hippocampal formation (HF) to the basolateral amygdala (BLA) play a role in Pavlovian fear conditioning to contextual conditional stimuli. We have used electrophysiological techniques to characterize neuronal transmission in these projections in urethane-anesthetized rats. Single-pulse electrical stimulation of the ventral angular bundle (VAB), which carries projections from the HF to the BLA, reliably evoked a biphasic extracellular field potential in the BLA that consisted of an early, negative and a late, positive component. The negative component of the field potential occurred at a short latency (3-8 msec), was both temporally and spatially correlated with VAB-evoked multiple-unit discharges in the BLA, and exhibited properties typical of a monosynaptic response. Infusion of lidocaine or glutamate receptor antagonists into the BLA attenuated VAB-evoked field potentials, indicating that they are generated by local synaptic glutamatergic transmission. Both paired-pulse stimulation and brief trains of high-frequency stimulation (HFS) induced a short-lasting facilitation of BLA field potentials, whereas longer and more numerous trains of HFS produced an enduring, NMDA receptor-dependent long-term potentiation (LTP) of the potentials. The induction of LTP was accompanied by a decrease in paired-pulse facilitation (PPF), suggesting a presynpatic modification underlying its expression. Electrolytic lesions placed in regions of the HF that project to the BLA or excitotoxic lesions placed in the BLA eliminated Pavlovian fear conditioning to a contextual conditional stimulus. The critical role of both structures in context conditioning implicates plasticity at HF-BLA synapses in this form of learning.

Taste-potentiated odor conditioning: Impairment produced by infusion of an N-methyl-D-aspartate antagonist into basolateral amygdala.

Two experiments examined the effects of infusing an N-methyl-D-aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonovalerate(d-APV), on taste-potentiated odor conditioning: a form of learning that is dependent on information processing in 2 sensory modalities. In Experiment 1, rats infused with d-APV were impaired in their acquisition of the potentiated learning to an odor cue. Expression of this learning and acquisition of a simple taste aversion remained intact following drug treatment. In Experiment 2, dose dependence and stereoselectivity were demonstrated for the antagonist compound. These results are consistent with previous studies demonstrating that either basolateral amygdala lesions, or treatment with NMDA antagonists, by other routes (systemic or intraventricular) produce selective deficits in taste-potentiated odor conditioning.

Taste-potentiated odor conditioning: impairment produced by infusion of an N-methyl-D-aspartate antagonist into basolateral amygdala.

Two experiments examined the effects of infusing an N-methyl-D-aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonovalerate(d-APV), on taste-potentiated odor conditioning: a form of learning that is dependent on information processing in 2 sensory modalities. In Experiment 1, rats infused with d-APV were impaired in their acquisition of the potentiated learning to an odor cue. Expression of this learning and acquisition of a simple taste aversion remained intact following drug treatment. In Experiment 2, dose dependence and stereoselectivity were demonstrated for the antagonist compound. These results are consistent with previous studies demonstrating that either basolateral amygdala lesions, or treatment with NMDA antagonists, by other routes (systemic or intraventricular) produce selective deficits in taste-potentiated odor conditioning.

Amphetamine-induced conditioned activity in rats: comparison with novelty-induced activity and role of the basolateral amygdala.

A within-subject design was used to investigate the behavioral and neural basis of the conditioned activity induced by amphetamine in male Wistar rats. In this design, conditioned activity was inferred when the activity of a given rat following a vehicle injection was greater in its amphetamine-paired environment (CS+) than in its vehicle-paired environment (CS-). Conditioned activity (a) did not change in magnitude with the number of conditioning sessions, (b) did not differ from the level of activity recorded during the first exposure to the CS- (novelty), (c) had an extinction rate that was similar to the rate of habituation to the CS-, and (d) was not impaired by a bilateral excitotoxic lesion of the basolateral amygdala. Results are discussed in light of the incentive conditioning and habituation theories of conditioned activity.

Attenuated hippocampal long-term potentiation in basolateral amygdala-lesioned rats

Possible involvement of the amygdaloid input in long-term potentiation (LTP) in the medial perforant path-dentate gyrus granule cell synapses in vivo was investigated by evaluating the effects of lesions of the amygdaloid nucleus. The dentate gyrus synaptic potential evoked by low-frequency test stimulation did not change following lesions of the basolateral and central amygdala. However, when tetanic stimulation (30 pulses at 60 Hz) was applied 60 min after lesioning of the ipsilateral basolateral amygdala, the magnitude of LTP was significantly attenuated. Since lesions of the ipsilateral central amygdala and the contralateral basolateral amygdala did not affect the dentate gyrus LTP, the attenuation of the dentate gyrus LTP is a specific effect of acute lesions of the ipsilateral basolateral amygdala. The basolateral amygdaloid lesions significantly attenuated both LTP induced by weak (20 pulses at 60 Hz) and strong (100 pulses at 100 Hz) tetanus, indicating that the effect of the lesions does not depend on the strength of tetanus applied to induce LTP. When the ipsilateral basolateral amygdala was destroyed after application of tetanus, it did not affect the established LTP. The attenuation of LTP was also observed after the basolateral amygdala-lesioned rats were allowed a recovery period of 2 weeks. This is the first report providing evidence that the ipsilateral basolateral amygdala modulates hippocampal synaptic plasticity in vivo.

Differential effects of excitotoxic lesions of the basolateral amygdala, ventral subiculum and medial prefrontal cortex on responding with conditioned reinforcement and locomotor activity potentiated by intra-accumbens infusions of d-amphetamine

Abstract The experiments reported here have investigated the impact on reward-related processes of lesioning the basolateral amygdala, ventral subiculum and prelimbic cortex which represent the major limbic sources of afferents to the ventral striatum. The results showed that, while lesions of the prelimbic cortex were without effect on the approach to a CS predictive of sucrose reinforcement and the acquisition of a new response with conditioned reinforcement, lesions of the other two structures significantly impaired both responses. However, there were important differences between the effects of basolateral amygdala and ventral subiculum lesions. Thus, lesions of the ventral subiculum completely abolished the locomotor response to intra-accumbens infusions of d-amphetamine, in addition to blocking the potentiative effect of the same treatment on responding with conditioned reinforcement. Lesions of the basolateral amygdala, by contrast, reduced the control over behaviour by a conditioned reinforcer, but not the potentiation of that control by intra-accumbens d-amphetamine except at the highest dose. Moreover, the locomotor response to d-amphetamine-induced increases in dopamine in the nucleus accumbens was unaffected by amygdala lesions over the dose range blocked by ventral subiculum lesions. The results suggest a rather selective effect of amygdala-ventral striatal interactions on processes subserving conditioned reinforcement and a more fundamental influence of ventral subiculum-ventral striatal interactions in mediating the psychomotor stimulant effects of d-amphetamine.

Place and taste aversion learning: Role of basal forebrain, parietal cortex, and amygdala

Animals with nucleus basalis magnocellularis (NBM), parietal cortex, dorsolateral frontal cortex, amygdala or control lesions were tested in a neophobia and taste aversion learning task. Only animals with basolateral amygdala lesions were impaired in taste aversion learning and in displaying neophobia to a novel flavor. This finding suggested a dissociation between the function of the NBM component of the basal forebrain cholinergic system and the amygdala. The same animals with NBM or control lesions were then tested for acquisition of a spatial navigation task using a dry-land version (cheese board) of the Morris water maze. Animals with NBM lesions were impaired in this task relative to control animals. Animals with parietal cortex lesions displayed a comparable deficit in the place navigation task. These findings suggest parallel functions for the NBM component of the basal forebrain system and the parietal cortex. The role of the NBM in mediating memory appears to be limited in that it does not play a role in all learning situations.

Lesions of the medial amygdala produce severe impairment of copulatory behavior in sexually inexperienced male rats

The effects of amygdaloid lesions on masculine copulatory behavior were examined in male rats. Sexually inexperienced male rats were castrated and subjected to bilateral lesions in one of the following areas: the medial amygdala, the cortical amygdala, or the basolateral amygdala. Three weeks later, all rats received implantation of silastic capsules containing testosterone. Then, four observations of copulatory behavior were carried out every 5 days following the implantation of testosterone. Rats with medial amygdala lesions showed a severe deficit of copulatory behavior, whereas rats with basolateral amygdala lesions showed no change in the performance of copulation. As for rats with cortical amygdala lesions, although their copulatory behavior was impaired, the effect was confined to a deficit in intromission and ejaculation responses. These findings suggest that the medial amygdala plays a critical role in regulating masculine sexual behavior in the rat.

Basolateral amygdala lesions block diazepam-induced anterograde amnesia in an inhibitory avoidance task.

This experiment examined the effects of diazepam (DZP) on acquisition and retention of an inhibitory avoidance response by rats with excitotoxic-induced lesions of central (CE), lateral (LAT), or basolateral (BL) amygdala nuclei. Sham-operated and lesioned rats received i.p. injections of DZP (2.0 mg per kg of body weight) 30 min before training in a continuous multiple-trial inhibitory avoidance task. Retention was tested 48 h later. Acquisition was not impaired by the lesions or the DZP. Retention was impaired in animals with CE and LAT lesions in comparison with sham-operated controls. DZP impaired retention in the sham-operated controls as well as CE- and LAT-lesioned animals but did not affect retention in animals with BL lesions. These findings indicate that the DZP-induced anterograde amnesia for inhibitory avoidance training is mediated through influences involving the BL amygdala nucleus.

Memory deficits following nucleus basalis magnocellularis lesions may be mediated through limbic, but not neocortical, targets

In order to test the contribution of the target areas of the nucleus basalis magnocellularis to the mediation of item and order recognition memory for spatial locations, one set of rats received lesions of the dorsolateral frontal cortex, parietal cortex, or basolateral amygdala after training in an order recognition memory task, whereas another set of animals received lesions of the nucleus basalis magnocellularis or basolateral amygdala in an item recognition memory task. Animals with basolateral amygdala lesions displayed a deficit for order recognition memory, but no deficit for item recognition memory, a pattern equivalent to that found for animals with nucleus basalis magnocellularis lesions. In contrast, animals with dorsolateral frontal cortex displayed no deficit, and animals with parietal cortex lesions displayed only a partial deficit for order recognition memory, results that differ from those found for animals with nucleus basalis magnocellularis lesions. It appears that the nucleus basalis magnocellularis influences item and order recognition memory for lists of spatial locations primarily through projections to limbic but not neocortical targets.

Central but not basolateral amygdala mediates memory for positive affective experiences

Rats were trained in an 8-arm radial maze on a task in which memory for magnitude of reinforcement was tested. Rats received a single trial per day consisting of a study phase and a test phase. In the study phase, the animals received 1 or 7 pieces of food on different arms of the maze. After the study phase, the rats were delayed for 5 s, 5 min or 15 min. After the delay the animals were allowed to choose between the two arms presented in the study phase. The correct response, leading to an additional reinforcement, was to select the arm in which the animal had received the 7 pieces of food. After learning this task to a criterion of 80% or better performance on blocks of 10 trials for each delay, the animals received electrolytic lesions of the basolateral or central amygdala. After recovery from surgery animals were tested at each delay. The results indicate that there were no deficits at any delay with basolateral amygdala lesions. In contrast, lesions of the central amygdala produced a marked deficit at the 5- and 15-min delays, but no deficit at the 5-s delay. Based on the assumption that in this task memory for magnitude of reinforcement is a function of the formation of reinforcement-spatial location associations resulting in the activation of affective experiences, it is concluded that the central but not basolateral amygdala is involved in the coding of positive affect information.

Effects of benzodiazepine and GABA antagonists on anticonflict effects of antianxiety drugs injected into the rat amygdala in a water-lick suppression test

In order to elucidate the role of the amygdala in rat conflict behavior in a water lick suppression test, we examined the effect of lesions of various nuclei of the amygdaloid complex on this behavior. An anticonflict effect was produced by a lesion of the anterior part of central and basolateral amygdala, and lesion to the posterior part of the central amygdala, but not by posterior of the basolateral amygdala or medial amygdala lesions. These results suggest that the amygdala, especially the anterior part of the central and basolateral nuclei, plays an important role in conflicting behavior of rats in the water lick test. In a second experiment, the effects of benzodiazepine- and GABA-antagonists on the anticonflict action of diazepam, zopiclone, and phenobarbital injected into the anterior part of central and basolateral amygdala were examined, also using a water lick suppression test. A dose-dependent anticonflict action was produced by systemic administration as well as by intra-amygdala injection of diazepam, zopiclone, lormetazepam, flurazepam and phenobarbital. The order of potency was lormetazepam greater than zopiclone greater than or equal to diazepam greater than flurazepam greater than or equal to phenobarbital for both routes of injection. The anticonflict effects of diazepam and zopiclone injected into the amygdala were completely reversed by Ro15-1788 and beta-CCM but not by bicuculline, while the anticonflict effect of phenobarbital was reversed by beta-CCM but not by Ro15-1788 or bicuculline. The present results strongly suggest that the anterior nuclei of central and basolateral amygdala are important sites of action of antianxiety drugs, and that an anticonflict action produced by intra-amygdala injection of benzodiazepines or barbiturate is mediated through the different receptor mechanisms.

Effects of anterior basolateral amygdala lesions on taste aversions produced by high and low oral doses of LiCl and lactose in the rat

Adult male hooded rats ( n = 12) with bilateral electrolytic lesions centred on the anterior basolateral amygdala (BLA) were given training using procedures meant to produce two different types of conditioned taste aversions (CTAs) to test whether the disruptive effects of such lesions on this form of learning were dependent upon the dosages of the illness-inducing agents used as unconditioned stimuli (UCSs). The CTAs were produced by either LiCl-induced toxicosis or lactose malabsorption. Comparison with sham-operated control subjects ( n = 8) indicated that the disruptive effects of the lesions were inversely related to the dosage level of LiCl but not lactose: whilst the lesions disrupted CTAs produced by a low i.p. dose of LiCl and by a low, but not a high, oral dose of LiCl, they did not alter CTA learning produced by either high or low oral doses of lactose. These results were interpreted as providing further evidence that BLA mediates only certain types of CTA learning.

Differential responsivity of corticosterone and prolactin to stress following lesions of the septum or amygdala: implications for psychoneuroendocrinology

Attempts to use neuroendocrine challenge tests to reflect suspected CNS dysfunction are popular, but frought with problems of interpretation. The dexamethasone suppression test of cortisol is thought to reflect limbic system function. Hormone responses to the triple bolus challenge test have also been reported to reflect limbic system dysfunction, but interpretation is dependent upon the hormone chosen for study. Challenge tests using prolactin have fallen out of favour because the final common pathway for its regulation lies outside the blood brain barrier. Thus, the ability of prolactin to reflect CNS and, specifically limbic system activity has been questioned. The present study undertook to determine corticosterone and prolactin responses in response to a variety of stimuli in rats that had selected limbic system damage following stereotoxically placed electrolic lesions. Surgical groups included: normal, sham-operated, septal lesion, cortico-medial amygdala lesion or baso-lateral amygdala lesion. All CNS damage was verified histologically. The stimuli chosen for neuroendocrine challenge were 3 minutes of exposure to, a novel environment, noise, ether vapour or cold water. These stimuli were chosen for their presumed level of neural input to the hypothalamic-pituitary axis. In the normal group, prolactin, but not corticosterone evidenced a differential response to the four stimuli. Following surgery, corticosterone responses to all stimuli were significantly influenced only in the septal lesion group. There was no interaction between the location of lesion with the type of stimuli used to elicit the corticosterone response. Prolactin, in contrast, evidenced significantly different responses depending on the location of the lesion, the type of stimulus and an interaction of these two variables. This level of differential responsiveness suggests that prolactin may have potential for diagnosis of limbic system dysfunction if appropriate test stimuli are employed to elicit its response.