N-methyl-D-aspartate lesions of the lateral and basolateral nuclei of the amygdaloid block fear-potentiated startle and shock sensitization of startle.

Destroyed cell bodies in the lateral and basolateral amygdaloid nuclei by local infusion of N-methyl-{d}-aspartate. Adjacent areas, such as the central amygdaloid nucleus, were largely spared. Lesions were carried out before training and testing (Exp 1) or after training but before testing (Exp 2). In both cases, the lesions completely blocked fear-potentiated startle (increased acoustic startle in the presence of a light previously paired with footshock). They also blocked increased startle after a series of footshocks, provided they damaged the most anterior part of the basolateral nucleus. It is suggested that the lateral or basolateral amygdaloid nuclei (or both) relay visual information to the central amygdaloid nucleus, which is also critical for fear-potentiated startle. In addition, activation of the most anterior part of the basolateral nucleus may be critical for processing shock information during fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrolytic lesions of the amygdala block acquisition and expression of fear-potentiated startle even with extensive training but do not prevent reacquisition.

Lesions of the amygdala have been shown to block the expression of fear-potentiated startle (increased acoustic startle in the presence of a cue previously paired with shock). In the present study, bilateral lesions of the central nucleus of the amygdala given after extensive training totally blocked the expression of fear-potentiated startle but did not prevent reacquisition. In contrast, when the lesions were made before any training, the lesioned rats did not show potentiated startle even with extensive training. Thus, the central nucleus of the amygdala normally seems to be required for the initial acquisition and expression of potentiated startle regardless of the degree of learning. However, reacquisition of potentiated startle can occur without the central nucleus, which implies the presence of a secondary brain system that can compensate for the loss of the central nucleus of the amygdala under some circumstances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term effects of neonatal damage to the hippocampal formation and amygdaloid complex on object discrimination and object recognition in rhesus monkeys (Macaca mulatta).

Rhesus monkeys with neonatal aspiration lesions of the hippocampal formation or the amygdaloid complex were tested on concurrent discrimination learning (24-hr intertrial interval [ITI]) at 3 months, on object recognition memory (delayed nonmatching-to-sample [DNMS]) at 10 months, and retested on both tasks at 6–7 years of age. Neonatal amygdaloid damage mildly impaired acquisition at the 24-hr ITI and the performance test of DNMS at both ages. In contrast, early hippocampal lesions impaired performance only on the longest lists of 10 items in DNMS in adult monkeys. Thus, early amygdala lesions appeared to have resulted in a greater object memory loss than early hippocampal lesions. However, in light of recent findings from lesion studies in adult monkeys, the object memory impairment after early amygdaloid lesions is better accounted for by damage to the entorhinal and perirhinal cortex than by damage to the amygdaloid nuclei. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociating the anti-fear effects of septal and amygdaloid lesions using two pharmacologically validated models of rat anxiety.

Compared the effects of septal and amygdaloid lesions in 2 models of rat anxiety. Septal lesions decreased burying behavior in the shock-probe burying test and increased open-arm exploration in the elevated plus-maze test, whereas amygdaloid lesions produced neither of these anxiolytic effects. However, amygdaloid lesions increased rats' contacts of the electrified probe, an anxiolytic effect not produced by septal lesions. Each of these distinct, anxiolytic effects of septal or amygdaloid lesions were displayed together in animals with lesions of both structures. Furthermore, the magnitude of these anxiolytic effects after combined lesions were comparable to their magnitude after individual lesions. Taken together, these results suggest that the amygdala and the septum independently control the expression of different fear-related behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Patterned (single) alternation in infant rats after combined or separate lesions of hippocampus and amygdala.

The role of the developing hippocampus and the amygdala on patterned (single) alternation (PA) in the infant rat was investigated in 4 experiments. In Exps 1 and 2, Ss were given 2 bilateral electrolytic hippocampal lesions or sham surgeries at 10 or 11 days of age and were trained 6 days later in a straight runway. In Exp 1, there were 120 trials in 1 day, with an 8-, a 15-, or a 30-s intertrial interval (ITI). PA learning occurred in lesion and sham Ss at the 8- and 15-s ITIs. In Exp 2, training was extended to 240 trials over 2 days, with a 30- or 60-s ITI. Sham and lesion Ss showed PA at the 30-s ITI, but the emergence of PA was delayed in the lesion pups at the 60-s ITI. In Exp 3, amygdaloid lesions had no effect on PA learning at the 8-s ITI. However, when Ss with hippocampal and amygdaloid lesions were trained at the 8-s ITI, the emergence of PA was delayed, and its size was reduced (Exp 4). Results argue for a role of the hippocampus in PA learning at long ITIs and suggest that, even in 16-day-old Ss exposed to an 8-s ITI, the combined hippocampal and amygdaloid lesion produces a deficit greater than either the hippocampal or the amygdaloid lesion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Limbic lesions and the energizing, aversive, and inhibitory effects of non-reward in rats.

Tested 30 male albino Wistar rats with bilateral lesions in the amygdala, septum, hippocampus, stria terminalis, and fornix on a multiple reinforcement schedule in which barpressing in one component was associated with VI reinforcement (S+) and the other with extinction (S–). Responses on a 2nd lever turned off S– for 5-sec periods during the extinction component. All groups, with the exception of Ss with amygdaloid lesions exhibited behavioral contrast. Ss with hippocampal or fornical lesions showed greater resistance to extinction. Response rates on the lever that turned off S– were higher after stria terminalis and septal lesions, whereas lower rates were obtained from Ss with amygdaloid lesions. It is concluded that amygdaloid lesions attenuate the energizing and aversive effects of nonreward, septal and stria terminalis lesions increase the aversive effects, and hippocampal and fornical lesions interfere with the inhibitory effects of nonreward. (French summary) (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Toxoplasma lymphadenitis. Analysis of cytologic and histopathologic criteria and correlation with serologic tests

Fear reactions of rats given bilateral lesions to the septum, hippocampus, or amygdala were compared with those of rats given sham lesions, in 2 animal models of anxiety: the shock-probe burying test and the elevated plus-maze test. Septal lesions produced anxiolytic effects in both tests (i.e., an increase in open-arm activity and a decrease in burying), whereas hippocampal and amygdaloid lesions produced neither of these effects. On the other hand, hippocampal and amygdaloid lesions impaired rats' passive avoidance of the electrified shock-probe, whereas septal lesions did not. These dissociations suggest that limbic structures such as the septum, amygdala, and hippocampus exert parallel but distinct control over different fear reactions.     

Syndrome produced by lesions of the amygdala in monkeys (Macaca mulatta).

12 male rhesus monkeys received bilateral stereotaxic lesions centered in the basolateral, lateral, and dorsal amygdala, or the temporal white matter lying adjacent to the lateral amygdala. Ss were compared with 4 others with control operations. Controls then received total amygdaloid lesions (AMX). AMX Ss exhibited the typical amygdaloid syndrome of hypoemotionality, meat eating, coprophagia, and excessive exploration. In contrast, Ss with subtotal amygdaloid lesions would not eat meat or feces, though they were more willing than controls to investigate inanimate objects. Extreme emotional changes after total amygdalectomy were found only in the S with the largest subtotal lesion. Only Ss that were hypoemotional showed a deficit in learning successive reversals of an object discrimination. This suggests that both the hypoemotionality and the successive reversal deficit arise from the same underlying dysfunction. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enhancement of acoustic startle by electrical stimulation of the amygdala.

The present study demonstrated that electrical stimulation of the amygdala enhanced the acoustic startle response. A 25-ms train of 0.1-ms pulses initiated 5 ms before the onset of a 20-ms noise burst significantly increased startle at currents from 40 to 400 μA. Electrode placements just medial to the amygdala (in the pathway connecting the amygdala to the brain stem) increased startle with the lowest currents. Startle was also increased in all animals with stimulation in the central, medial, and intercalated nuclei of the amygdala. Stimulation in areas surrounding the amygdaloid complex was ineffective. In a second experiment, paired pulses with interpulse intervals between 0.1 and 20.0 ms delivered to the amygdala demonstrated that the stimulated axons had a distribution of refractory periods between 0.6 and 1.0 ms. This suggests that the population of neurons which subserves the enhancement of acoustic startle is fairly homogeneous and has small, myelinated axons. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Taste-potentiated odor aversion learning: Role of the amygdaloid basolateral complex and central nucleus.

Examined the relative contributions of the amygdaloid basolateral complex (ABL) and central nucleus (CN) to taste-potentiated odor aversion (TPOA) learning, an associative learning task that is dependent on information processing in 2 sensory modalities. In Exp 1, rats with neurotoxic lesions of these systems were trained on the TPOA task by presenting a compound taste–odor conditioned stimulus (CS), which was followed by LiCl administration. Results showed that ABL damage caused an impairment in potentiated odor aversion learning but no deficit in the conditioned taste aversion. In contrast, rats with CN damage learned both tasks. Exp 2 examined the effects of ABL damage on TPOA and odor discrimination learning. The odor discrimination procedure used a place preference task to demonstrate normal processing of olfactory information. Results indicated that although ABL-lesioned animals were impaired on TPOA, there was no deficit in odor discrimination learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Visual input and lateralization of brain function in learning in the chick

Several lines of evidence (biochemical, neuroanatomical, electrophysiological, and behavioural) have indicated a critical role for the intermediate medial hyperstriatum ventrale of the chick forebrain in the acquisition of a passive avoidance response. Previous lesion studies indicated that bilateral or left, but not right, pretraining intermediate medial hyperstriatum ventrale lesions interfere with the acquisition of this task. We have further analysed this asymmetrical involvement of the intermediate medial hyperstriatum ventrale by use of a monocular learning protocol and intermediate medial hyperstriatum ventrale lesions (sham, bilateral, or unilateral). The results indicated that there is interocular transfer of information of passive avoidance learning between the two eye systems, with a tendency to be more successful from the right eye system to the left than in the opposite direction. As in binocular conditions, bilateral pretraining intermediate medial hyperstriatum ventrale lesions impair learning in monocularly trained animals. Unilateral lesions to either left or right monocularly trained experimental animals resulted in amnesia when they were made to the right intermediate medial hyperstriatum ventrale and the chicks were trained/tested with the left eye open. These results indicate that, although right intermediate medial hyperstriatum ventrale lesions do not result in amnesia in binocular animals, this region is capable of participating in memory acquisition processes. They also suggest a connection between lateralization of intermediate medial hyperstriatum ventrale function in passive avoidance learning and the behavioural and structural visual asymmetries known to occur in chicks.     

Amygdaloid complex lesions differentially affect retention of tasks using appetitive and aversive reinforcement.

Hypothesized that the amygdaloid complex (AC) is involved in the formation of stimulus–reward associations. A series of experiments (1A–2C) directly compared the effects of lesions (produced by injection of the excitotoxin N-methyl-{D}-aspartic acid) on 1-trial appetitive (APP) and 1-trial aversive (AV) learning in rats. Exps 1A and 1B, which used different degrees of reinforcement, showed no effect of lesions on the APP task, whereas acquisition of the AV task was significantly impaired. This impairment depended on the nature of the AV reinforcement used: Impairment was seen when a highly AV stimulus (footshock) was used but not when a less AV stimulus (0.2% quinine solution) was used. Control experiments showed that the effect of lesions was not due to reduced sensitivity to the footshock. In Exp 2, a novel odor conditioning task examined further the effect of AC lesions on acquisition of APP and AV stimulus–reinforcement associations. As in Exp 1, AC lesions impaired learning of the AV association but did not significantly influence the APP association. Although the AC may be involved in some APP rewarded learning, the differential effect of AC lesions on AV rewarded learning suggests a role in learning beyond the formation of stimulus–reinforcement associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the bed nucleus of the stria terminalis block sensitization of the acoustic startle reflex produced by repeated stress, but not fear-potentiated startle

1. The effects of lesions of the bed nucleus of the stria terminalis (BST) on the acquisition of conditioned fear were examined. In Experiment 1, BST lesions did not block acquisition of fear-potentiated startle to an explicit visual conditioned stimulus (CS) over 20 days of training. However, BST lesions blocked a gradual elevation in baseline startle also seen over the course of training. 2. The gradual increase in baseline startle was replicated in Experiment 2 without the presence of an explicit CS, using unoperated subjects. Experiment 2 showed that the elevation was due to repetitive exposure to shock, because unshocked control subjects did not show any elevation over sessions. 3. In Experiment 3, lesions of the BST did not disrupt rapid sensitization of the startle reflex by footshock, showing that different neural substrates underlie sensitization of startle by acute and chronic exposure to footshock. 4. These data indicate that the BST, despite its anatomical continuity with the amygdala, is not critically involved in the acquisition of conditioned fear to an explicit CS. Nevertheless, the BST is involved in mediating a stress-induced elevation in the startle reflex. This suggests that the BST and the CeA, which constitute part of the "extended amygdala" have complementary roles in responses to stress.     

Differences in spatial discrimination reversal learning between two inbred mouse strains following specific amygdaloid lesions.

Tested reversal learning for 2 groups of 85 male C57BL/6J and BALB/cJ mice following a bilateral lesion in either the basolateral, central, lateral, medial, or cortical nucleus of the amygdala. On the 2nd reversal, C57BL/6J Ss with a lesion in the lateral nucleus performed less well than intact controls and operated controls. The BALB/cJ Ss with a lesion in the cortical nucleus performed less well on the 1st reversal than these 2 control groups. Data indicate that effects of specific amygdaloid lesions on learning are not necessarily the same for all strains or stocks within a species, and that lesions simultaneously involving many nuclei may be of limited usefulness in understanding the relationship of the amygdala to reversal learning. (27 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociations among the anxiolytic effects of septal, hippocampal, and amygdaloid lesions.

Fear reactions of rats given bilateral lesions to the septum, hippocampus, or amygdala were compared with those of rats given sham lesions, in 2 animal models of anxiety: the shock-probe burying test and the elevated plus-maze test. Septal lesions produced anxiolytic effects in both tests (i.e., an increase in open-arm activity and a decrease in burying), whereas hippocampal and amygdaloid lesions produced neither of these effects. On the other hand, hippocampal and amygdaloid lesions impaired rats' passive avoidance of the electrified shock-probe, whereas septal lesions did not. These dissociations suggest that limbic structures such as the septum, amygdala, and hippocampus exert parallel but distinct control over different fear reactions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of the dorsal periaqueductal gray in the loss of fear-potentiated startle accompanying high footshock training.

The amplitude of acoustic startle is markedly enhanced by cues signaling moderately intense footshocks but, surprisingly, not by cues signaling higher intensity footshocks. Previous findings suggest that the ineffectiveness of high footshock training may involve activation of the dorsal periaqueductal gray (PAG). As a means of evaluating this possibility, rats trained with moderate (0.6 mA) footshocks were later tested after intra-PAG infusion of an excitatory nontoxic dose of kainic acid. Kainic acid significantly reduced fear-potentiated startle relative to vehicle controls. In a 2nd experiment, the effect of dorsal PAG lesions on fear-potentiated startle to cues paired with 0.6-mA and 1.6-mA footshocks was evaluated. Dorsal PAG lesions prevented the disruptive effects of high footshock training. Together, these results suggest that dorsal PAG activation mediates the loss of potentiated startle accompanying high footshock training. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the amygdala, but not of the cerebellum or red nucleus, block conditioned fear as measured with the potentiated startle paradigm.

In Exp I, 97 male Sprague-Dawley albino rats were given 10 light–shock pairings on 2 successive days. At 24–48 hrs following training, groups of Ss received bilateral transection of the cerebellar peduncles, bilateral lesions of the red nucleus (which receives most of the cerebellar efferents), or bilateral lesions of the central nucleus of the amygdala. Controls were sham operated. At 3–4 days after surgery, Ss were tested for potentiated startle (PS [increased acoustic startle in the presence of the light previously paired with shock]). PS was blocked by lesions of the central nucleus of the amygdala but not by transection of the cerebellar peduncles or lesions of the red nucleus. Exp II, in which a visual prepulse test was used with 14 Ss, indicated that the blockade of PS observed in Ss with amygdala lesions could not be attributed to optic tract damage. Exp III, with 20 Ss, demonstrated that the absence of potentiation in Ss with amygdala lesions was not simply due to a lowered startle level ceiling, because these Ss could show increased startle with increased stimulus intensity and with administration of intraperitoneal strychnine, (0.75 mg/kg), a drug that increases startle. Results are consistent with the hypothesis that the amygdala is involved in fear conditioning. (64 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the perirhinal cortex interfere with conditioned excitation but not with conditioned inhibition of fear.

Posttraining lesions of the perirhinal cortex (Prh) have been shown to interfere with the expression of fear. This study assessed whether Prh lesions would also disrupt the inhibition of fear as measured with conditioned inhibition of fear-potentiated startle. Following light + shock, noise→ light-no shock conditioned-inhibition training, rats were given Prh lesions. The lesions interfered with the expression of fear-potentiated startle to the light. To assess whether conditioned inhibition was affected, the rats were given light + retraining without additional noise→ light - training. The noise-conditioned inhibitor retained its ability to inhibit fear-potentiated startle to the retrained light. These results suggest that the areas of the Prh that are essential for the initial expression of conditioned fear are not important for the expression of conditioned inhibition of fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Does the bed nucleus of the stria terminalis mediate fear behaviors?

The bed nucleus of the stria terminalis (BNST) has been implicated in autonomic and hormonal reactions to fearful stimuli, but its role in behavioral reactions to these stressors is less clear. This is puzzling, because 2 closely related areas, the septum and the amygdala, have been repeatedly implicated in fear behaviors. To investigate further, the behavioral effects of BNST lesions were compared to those of septal and amygdaloid lesions in 2 models of rat anxiety: the plus-maze and shock-probe tests. Septal lesions inhibited rats' open-arm avoidance in the plus-maze and suppressed burying of the shock-probe, whereas amygdaloid lesions specifically inhibited shock-probe avoidance. However, BNST lesions produced none of these anti-fear effects; thus, its involvement in the behavioral expression of fear is questionable. (PsycINFO Database Record (c) 2010 APA, all rights reserved)