Basolateral amygdala inactivation impairs learned (but not innate) fear response in rats

Numerous studies have suggested that the amygdala is involved in the formation of aversive memories, but the possibility that this structure is merely related to any kind of fear sensation or response could not be ruled out in previous studies. The present study investigated the effects of bilateral inactivation of the amygdaloid complex in rats tested in the plus-maze discriminative avoidance task. This task concomitantly evaluates aversive memory (by discrimination of the two enclosed arms) and innate fear (by open-arm exploration). Wistar rats (3-5 months-old) were implanted with bilateral guide cannulae into basolateral amygdala. After surgery, all subjects were given 1 week to recover before behavioral experiments. Afterwards, in experiment 1, 15 min prior to training, 0.5 μl of saline or muscimol (1 mg/ml) was infused in each side via microinjection needles. In experiment 2 the animals received injections immediately after the training session and in experiment 3 rats were injected prior to testing session (24 h after training). The main results showed that (1) pre-training muscimol prevented memory retention (evaluated by aversive arm exploration in the test session), but did not alter innate fear (evaluated by percent time in open arms); (2) post-training muscimol impaired consolidation, inducing increased percent in aversive arm exploration in the test session and (3) pre-testing muscimol did not affect retrieval (evaluated by aversive enclosed arm exploration in the test session). The results suggest that amygdala inactivation specifically modulated the learning of the aversive task, excluding a possible secondary effect of amygdala inactivation on general fear responses. Additionally, our data corroborate the hypothesis that basolateral amygdala is not the specific site of storage of aversive memories, since retention of the previously learned task was not affected by pre-testing inactivation.     

Multiple spatial learning strategies in goldfish (Carassius auratus)

There is a considerable amount of evidence that mammals and birds can use different spatial learning strategies based on multiple learning and memory systems. Unfortunately, only a few studies have investigated spatial learning and memory mechanisms in other vertebrates. This study aimed to identify the strategies used by goldfish to solve two different spatial tasks in a series of three experiments. In experiment 1, two groups of goldfish (Carassius auratus) were trained either in a spatial constancy task (SC), in which visual cues signalled the goal indirectly, or in a directly cued task (DC) in which similar cues signalled the goal directly. Transfer tests were conducted to study the effects of discrete cue deletion on the performance in both tasks. In these transfer tests the performance of the animals trained in the DC task dropped to chance level when the cue that signalled the goal directly was removed. In contrast, the removal of any single cue did not disrupt SC performance. In experiment 2, fish trained in the SC or the DC task were trained with the goal reversed. Goldfish in the SC group needed fewer sessions to master the reversal task than DC animals. Finally, experiment 3 investigated the effects of a substantial modification of the geometrical features of the apparatus on the performance of animals trained in the SC or in the DC condition. The performance of DC goldfish was not affected, whereas the same change disrupted performance in the SC animals despite the presence of the visual cues. These results suggest that there are separate spatial learning and memory systems in fish. Whereas the DC animals used a typical guidance strategy, relying only on the cue that signalled the goal directly, SC fish relied on a strategy with the properties of an actual spatial mapping system. Thus, the comparative approach points to the generality of these learning strategies among vertebrates. Received: 10 October 1998 / Accepted after revision: 16 April 1999     

Auditory frequency generalization in the goldfish (Carassius auratus)

Auditory frequency generalization in the goldfish was studied at five points within the best hearing range through the use of classical respiratory conditioning. Each experimental group received single-stimulus conditioning sessions at one of five stimulus frequencies (100, 200, 400, 800, and 1600 Hz), and were subsequently tested for generalization at eight neighboring frequencies. All stimuli were presented 30 db above absolute threshold. Significant generalization decrements were found for all subjects. For the subjects conditioned in the range between 100 and 800 Hz, a nearly complete failure to generalize was found at one octave above and below the training frequency. The subjects conditioned at 1600 Hz produced relatively more flat gradients between 900 and 2000 Hz. The widths of the generalization gradients, expressed in Hz, increased as a power function of frequency with a slope greater than one.     

Zinc transporter 3 is involved in learned fear and extinction, but not in innate fear

Synaptically released Zn2+ is a potential modulator of neurotransmission and synaptic plasticity in fear-conditioning pathways. Zinc transporter 3 (ZnT3) knock-out (KO) mice are well suited to test the role of zinc in learned fear, because ZnT3 is colocalized with synaptic zinc, responsible for its transport to synaptic vesicles, highly enriched in the amygdala-associated neural circuitry, and ZnT3 KO mice lack Zn2+ in synaptic vesicles. However, earlier work reported no deficiency in fear memory in ZnT3 KO mice, which is surprising based on the effects of Zn2+ on amygdala synaptic plasticity. We therefore reexamined ZnT3 KO mice in various tasks for learned and innate fear. The mutants were deficient in a weak fear-conditioning protocol using single tone-shock pairing but showed normal memory when a stronger, five-pairing protocol was used. ZnT3 KO mice were deficient in memory when a tone was presented as complex auditory information in a discontinuous fashion. Moreover, ZnT3 KO mice showed abnormality in trace fear conditioning and in fear extinction. By contrast, ZnT3 KO mice had normal anxiety. Thus, ZnT3 is involved in associative fear memory and extinction, but not in innate fear, consistent with the role of synaptic zinc in amygdala synaptic plasticity.     

Sex differences in response to an observational fear conditioning procedure

The present study evaluated sex differences in observational fear conditioning using modeled “mock” panic attacks as an unconditioned stimulus (UCS). Fifty-nine carefully prescreened healthy undergraduate participants (30 women) underwent 3 consecutive differential conditioning phases: habituation, acquisition, and extinction. It was expected that participants watching a confederate display mock panic attacks (UCS) paired with a previously neutral stimulus (CS⁺) would learn to respond fearfully to the CS⁺, but not to the CS⁻ (i.e., a stimulus never associated with displays of panic). Women also were expected to report more distress and ratings of panic to the CS⁺ than the CS⁻ compared to men, but no sex differences were anticipated on autonomic indices of conditioning (i.e., electrodermal responses). Consistent with expectation, aversive conditioning was demonstrated by greater magnitude electrodermal and verbal-evaluative (e.g., subjective units of distress scale, panic ratings) responses to the CS⁺ over the CS⁻, with women reporting more distress to the CS⁺ over the CS⁻, but not greater autonomic conditioning, compared to men. Overall, the results support the notion that modeled panic attacks can serve as a potent UCS for both men and women. Discussion focuses on sex differences in observational fear conditioning and its relation to the clinical presentation of anxiety disorders.     

Temporal discrimination learning of operant feeding in goldfish (Carassius auratus)

Operant temporal discrimination learning was investigated in goldfish. In the first experiment, there was a fixed daily change in illumination. Eight subjects were trained to operate a lever that reinforced each press with food. The period during which responses were reinforced was then progressively reduced until it was 1 hr in every 24. The final 1-hr feeding schedule was maintained over 4 weeks. The feeding period commenced at the same time each day throughout. The food dispensers were then made inactive, and a period of extinction ensued for 6 days. The pattern of responding suggested that the fish were able to exhibit temporal discrimination in anticipation of feeding time. This pattern of responding persisted for a limited number of days during the extinction procedure. The second experiment produced evidence that operant temporal discrimination could develop under continuous illumination.     

A developmental dissociation in reinstatement of an extinguished fear response in rats

Recently, studies from our laboratory have shown that 16-day-old rats, in contrast to 23-day-old rats, fail to show either ABA renewal or recovery of an extinguished fear response following a pre-test injection of FG7142 [Kim, J. H. & Richardson, R. (2007). A developmental dissociation of context and GABA effects on extinguished fear in rats. Behavioral Neuroscience; Yap & Richardson, unpublished data]. The present study, using freezing as a measure of learned fear, extends these findings by examining whether there is a developmental difference in susceptibility to reinstatement following extinction. 16- and 23-day-old rats were trained to fear a white-noise conditioned stimulus (CS) by pairing it with a shock unconditioned stimulus (US). This fear was subsequently extinguished by non-reinforced presentations of the CS. Some rats received a post-extinction Reminder which consisted of a single presentation of a reduced-intensity US. Experiments 1 and 2 demonstrated that this Reminder was effective in reinstating extinguished fear in 23-day-olds, and that this reinstatement effect was context-specific in rats this age. In contrast, 16-day-old rats failed to show the reinstatement effect in either experiment. The failure to observe a post-extinction reinstatement effect in the 16-day-olds was not due to a general ineffectiveness of the Reminder treatment at this age because it did alleviate spontaneous forgetting in rats this age (Experiment 3). Taken together, the results suggest that fundamentally different processes may mediate extinction early in development compared to later in development.     

Encoding of geometric and featural spatial information by goldfish (Carassius auratus)

Goldfish (Carassius auratus) were trained in different place-finding tasks as a means of analyzing their ability to encode the geometric and the featural properties of the environment. Results showed that goldfish could encode and use both geometric and featural information to navigate. Goldfish trained in a maplike, or relational, procedure encoded both types of information in a single representation. In contrast, fish trained in a directly cued procedure developed 2 independent and competing strategies. These results suggest that the geometric properties of the spatial arrangement and discrete landmarks are sensitive to encoding in a maplike or relational system, whereas different sources of spatial information are encoded in a single and flexible representation of the environment.     

Different ways of encoding geometric information by goldfish (Carassius auratus)

On the basis of results of a probe trial in 2 different experiments, K. Cheng (2005) has proposed a common mechanism for orientation in fish trained in both a map-like or relational procedure and a directly cued procedure. However, K. Cheng's model is inconsistent with previous results of goldfish (Carassius auratus) trained in these 2 tasks. Given that K. Cheng's proposal assumes that fish choose the goal by using a matching strategy in which they try to match as many properties as possible, including geometric and featural properties, future research is necessary to clarify what properties of the environmental space are codified and used for navigation.     

Sensitivity and response bias in fear of spiders

According to cognitive theories of anxiety, phobic patients are searching the environment for threatening stimuli, and detecting them rapidly. However, previous studies failed to find a lowered perceptual threshold for threatening stimuli in specific phobias. Therefore, two experiments applying a signal detection paradigm were conducted. Highly spider fearful and nonfearful participants were asked to decide whether a picture of a spider, beetle, or butterfly was presented. In both experiments, spider fearfuls were not better at detecting spiders, or any other animal, than healthy controls. Instead, spider fearfuls were more liberal in assuming that they had seen a spider or a beetle. In accord with earlier studies, these results suggest that spider phobics may exhibit an interpretation bias rather than improved detection of threat.     

Habituation and sensitization of aggression in bullfrogs (Rana catesbeiana): testing the dual-process theory of habituation

The aggressive response of male bullfrogs (Rana catesbeiana) habituates with repeated broadcasts of acoustic stimuli simulating a new territorial neighbor. The effects of stimulus repetition rate and stimulus intensity on bullfrog aggressive responses were tested in a field experiment designed to test the assumptions of a dual-process theory of habituation. Synthetic advertisement calls were broadcast at 2 repetition rates and 2 intensities in a factorial design. Bullfrogs were more aggressive at the higher stimulus intensity at both repetition rates. Aggressive responses habituated more slowly at the higher stimulus intensity and slower repetition rate compared with other treatments. Several biotic and abiotic factors had small or negligible effects on aggressive responses. Although consistent with the operation of 2 opposing processes, habituation and sensitization, the data provide only partial support for the assumptions of dual-process theory.