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Results for “fear conditioning”

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PubMed1996

N-methyl-D-aspartate receptors in the basolateral amygdala are required for both acquisition and expression of conditional fear in rats.

Three experiments examined the effects of intra-amygdaloid infusions of an N-methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovalerate (APV), on contextual fear conditioning in rats. In Experiment 1, APV infusion into the basolateral amygdala (BLA), before training, disrupted the acquisition of contextual fear. In Experiment 2, APV produced a disruption of both the acquisition and expression of contextual fear. This blockade of contextual fear was not state dependent, not due to a shift in footshock sensitivity, and not the result of increased motor activity in APV-treated rats. In Experiment 3, fear conditioning was not affected by a posttraining APV infusion into the BLA. These results indicate that NMDA receptors in the BLA are necessary for both the acquisition and expression of Pavlovian fear conditioning to contextual cues in rats.

2-Amino-5-phosphonovalerate↗
PubMed2006

Effects of stress and sex on acquisition and consolidation of human fear conditioning.

We examined the relationship between stress hormone (cortisol) release and acquisition and consolidation of conditioned fear learning in healthy adults. Participants underwent acquisition of differential fear conditioning, and consolidation was assessed in a 24-h delayed extinction test. The acquisition phase was immediately followed by an 11-min psychosocial stress period (arithmetic test combined with a public speech). Salivary cortisol was sampled at various time points before and after acquisition and retention of fear conditioning. Results showed two effects of endogenous cortisol. Post-acquisition cortisol correlated with fear acquisition in male but not female participants. In addition, post-acquisition cortisol correlated with consolidation of fear but only in those participants with high cortisol levels. We conclude that in the short term, a robust and sexually dimorphic relationship exists between fear learning and stress hormone levels. For those participants whose fear learning is accompanied by high stress hormone levels, a long-term relationship exists between cortisol release and memory consolidation. These short-term and long-term effects may relate to the differential involvement of mineralocorticoid and glucocorticoid receptor subtypes, respectively. The findings have implications for understanding the role of stress, sex, and hormones in different stages of fear learning and memory.

Adult↗
PubMed2006

Generalization of amygdala LTP and conditioned fear in the absence of presynaptic inhibition.

Pavlovian fear conditioning, a simple form of associative learning, is thought to involve the induction of associative, NMDA receptor-dependent long-term potentiation (LTP) in the lateral amygdala. Using a combined genetic and electrophysiological approach, we show here that lack of a specific GABA(B) receptor subtype, GABA(B(1a,2)), unmasks a nonassociative, NMDA receptor-independent form of presynaptic LTP at cortico-amygdala afferents. Moreover, the level of presynaptic GABA(B(1a,2)) receptor activation, and hence the balance between associative and nonassociative forms of LTP, can be dynamically modulated by local inhibitory activity. At the behavioral level, genetic loss of GABA(B(1a)) results in a generalization of conditioned fear to nonconditioned stimuli. Our findings indicate that presynaptic inhibition through GABA(B(1a,2)) receptors serves as an activity-dependent constraint on the induction of homosynaptic plasticity, which may be important to prevent the generalization of conditioned fear.

Amygdala↗
PubMed1997

Contextual conditioned fear blocks the induction but not the maintenance of lateral septal LTP in behaving mice.

High-frequency stimulation (HFS) of the fimbria induces long-term potentiation (LTP) in the lateral septum. This study was aimed at investigating the effect of contextual fear conditioning on septal LTP with the use of behaving C57 BL/6 mice as subjects. For the acquisition of contextual fear conditioning, animals were placed in a conditioning chamber, where they were subjected to footshocks (FSs, 0.6 mA); the following day (retention), animals were reexposed to the chamber. Animals from the first group received HFS in their home cages before being submitted to conditioning; animals from the second group were first submitted to conditioning before receiving HFS during reexposure to the conditioning chamber; animals from the third group were submitted to the same regimen as those from the second group, except that no FS was delivered in the conditioning chamber; and animals from the fourth group received FS in the conditioning chamber but were maintained in their home cages the day after for LTP induction. Before conditioning, animals from the first group, placed in a familiar context (home cage), displayed an LTP of the N3 wave of septal field potential. After conditioning, reexposure of these animals to the conditioning chamber produced a transient decrease in the amplitude of N3 but did not interfere with the duration of maintenance of LTP. Conversely, in animals from the second group, when HFS was applied during reexposure to the conditioning chamber the induction of LTP was totally blocked. However, mice from the two other groups (3rd and 4th) displayed normal levels of LTP. Taken together with previous findings, these data suggest that contextual conditioned fear may interfere with certain forms of learning via blockade of hippocampal-septal LTP.

Animals↗
PubMed2003

Functional MRI of human amygdala activity during Pavlovian fear conditioning: stimulus processing versus response expression.

Although laboratory animal studies have shown that the amygdala plays multiple roles in conditional fear, less is known about the human amygdala. Human subjects were trained in a Pavlovian fear conditioning paradigm during functional magnetic resonance imaging (fMRI). Brain activity maps correlated with reference waveforms representing the temporal pattern of visual conditional stimuli (CSs) and subject-derived autonomic responses were compared. Subjects receiving paired CS-shock presentations showed greater amygdala activity than subjects receiving unpaired CS-shock presentations when their brain activity was correlated with a waveform generated from their behavioral responses. Stimulus-based waveforms revealed learning differences in the visual cortex, but not in the amygdala. These data support the view that the amygdala is important for the expression of learned behavioral responses during Pavlovian fear conditioning.

Adult↗
PubMed1996

Partial disruption of fear conditioning in rats with unilateral amygdala damage: correspondence with unilateral temporal lobectomy in humans.

Conditioned fear in rats was assessed for the effects of pretraining amygdala lesions (unilateral vs. bilateral) across unconditioned stimulus (US) modalities (white noise vs. shock). In contrast to sham controls, unilateral amygdala lesions significantly reduced conditioned freezing responses, whereas bilateral amygdala lesions resulted in a nearly complete lack of freezing to both the conditioned stimulus (CS) and the context. The lesion effects were more pronounced for CS conditioning but were consistent across US modalities. It was concluded that white noise can serve as an effective US and that unilateral amygdala lesions attenuate but do not eliminate conditioned fear in rats. The results support our interpretation of a recent fear conditioning study in humans (K. S. LaBar, J. E. LeDoux, D. D. Spencer, & E. A. Phelps, 1995).

Animals↗
PubMed1997

Amphetamine sensitization enhances regional c-fos expression produced by conditioned fear.

Chronically administered amphetamine can result in a paranoid psychosis that can be re-induced in former amphetamine abusers by psychological stressors. In an attempt to investigate the neurobiological correlates of this phenomenon, the present study examined the effects of prior D-amphetamine sensitization on regional c-fos expression induced by a psychological stressor. Rats received intermittent footshock in a distinctive environment for 30 min/day for three days. Three days after the last fear conditioning session, the animals received injections of saline or D-amphetamine (4 mg/kg, i.p.) once every second day for 16 days (eight injections in total). After a 14-day drug abstinent period, the animals were placed in the fear conditioning apparatus but without footshock. The amphetamine sensitization procedure significantly enhanced the effects of conditioned fear on c-fos expression in several brain regions. These included the cingulate cortex area 3, agranular insular cortex (layers 2 and 3), claustrum, piriform cortex, the shell region of the nucleus accumbens, medial striatum, ventral lateral septum, and CA3 and polymorphic layer of the hippocampal formation. These results indicate that D-amphetamine sensitization can have long-lasting effects on the neural circuitries activated by conditioned stressors.

Animals↗
PubMed2006

Entorhinal cortex lesions disrupt fear conditioning to background context but spare fear conditioning to a tone in the rat.

Recent studies have shown that the integrity of the entorhinal cortex (EC) is not required for simple contextual conditioning. In background contextual conditioning, i.e., when a phasic cue is present during training, the involvement of the EC is still a matter of debate. Therefore, the present work further examines whether the EC is required for background contextual conditioning using a tone as the phasic cue. Rats sustaining either excitotoxic lesions of the EC or sham-lesions were trained with one of two procedures differing with respect to the predictive value of the tone: a paired procedure in which the tone perfectly predicts shock occurrence and overshadows context, and an unpaired procedure in which the predictive value of the tone is reduced. Conditioned fear was assessed by freezing responses during conditioning, reexposure to the training context, and reexposure to the tone in a new context. Postshock freezing was reduced in rats with entorhinal lesions. In all rats trained with the paired procedure, freezing to the context was low and freezing to the tone was high, suggesting that the tone has overshadowed the context during the conditioning session. The reverse pattern was observed with the unpaired procedure in sham-operated rats. In rats with entorhinal lesions trained with the unpaired procedure, freezing responses to the context was markedly reduced. In a new context, however, entorhinal-lesioned rats showed higher freezing scores than those of sham-lesioned rats. Freezing to the tone was unaffected by the lesion irrespective of the tone's predictive value. As a whole, these results support the notion that the EC is required for normal background contextual freezing.

Acoustic Stimulation↗
PubMed1984

Epinephrine enables Pavlovian fear conditioning under anesthesia.

Rats under Pavlovian defensive conditioning (noise paired with shock) while under general anesthesia. Peripheral administration of epinephrine (0.01 to 1.0 milligram per kilogram of body weight) during training resulted in the acquisition of conditioned fear, as shown 10 days later by conditioned suppression of water drinking. Analysis of heart rate and measurement of reflexes during training indicated that epinephrine did not lighten the state of anesthesia. These results indicate that epinephrine enables the learning of conditioned fear in the anesthetized brain.

Anesthesia, General↗
PubMed1986

Effects of contingency violations on the extinction of a conditioned fear inhibitor and a conditioned fear excitor.

Rats were used in a conditioned-suppression paradigm to assess the effects of contingency variations on responding to a conditioned inhibitor (CS-) and a conditioned excitor (CS+). In Experiment 1, various unconditioned stimulus (US) frequencies were equated across the presence and absence of a CS- in the context of either background cues (continuous-trial procedure) or an explicit neutral event (discrete-trial procedure). With both procedures, a CS-alone treatment enhanced inhibition, whereas treatments involving 50% or 100% reinforcement for the CS- eliminated inhibition without conditioning excitation to that CS. The latter outcome also occurred in Experiment 2, with discrete-trial training equating considerably reduced US frequencies for the presence and absence of the CS-. In further evidence that inhibition was eliminated without conditioning excitation to the CS-, Experiment 3 showed that a novel CS did not acquire excitation when 25%, 50%, or 100% reinforcement was equated across the presence and absence of that CS in the context of a discrete-trial event. Using the procedures of Experiment 1, Experiment 4 showed that a CS+ was extinguished by a CS-alone treatment but was substantially maintained by treatments involving 50% or 100% uncorrelated reinforcement. These effects for a CS+ and a CS- implicate CS-US contiguity, rather than contingency, as the factor determining the extinction of a CS.

Animals↗
PubMed2002

Mechanisms of Pavlovian fear conditioning: has the engram been located?

Uncertainty persists as to whether the amygdala is a crucial site of plasticity for classically conditioned fear or merely a sensory relay to structures generating fear responses. A recent Nature study suggests that associative synaptic changes take place in neurons of the amygdala during fear conditioning, and that these changes require dopamine-mediated modulation. Nevertheless, these findings do not prove that the amygdala is a sufficient site of plasticity for fear memory.

Amygdala↗
PubMed1999

Contribution of ventrolateral prefrontal cortex to the acquisition and extinction of conditioned fear in rats.

The ventrolateral, agranular insular portion of prefrontal cortex (PFC) in rats is involved in visceral functions and has been shown to be involved in emotional processes. However, its contribution to aversive learning has not been well defined. Classical fear conditioning has been a powerful tool for illuminating some of the primary neural structures involved in aversive emotional learning. We measured both the acquisition and the extinction of conditioned fear following lesions of the ventrolateral PFC of rats. Lesions reduced fear reactivity to contextual stimuli associated with conditioning without affecting CS acquisition, and had no effect on response extinction. Ventrolateral PFC may normally be involved in the processing of contextual information while not being directly involved in extinction processes within the aversive domain.

Animals↗
PubMed2002

MK-801 disrupts acquisition of contextual fear conditioning but enhances memory consolidation of cued fear conditioning.

The effects of pre-training or post-training subcutaneous injections of multiple doses of the non-competitive NMDA-receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) on cued and contextual fear conditioning were examined in F344 rats. Pre-training injections of MK-801 (0.3 and 1.0 mg/kg) disrupted contextual fear conditioning but not cued fear conditioning. Post-training injections of MK-801 did not disrupt cued or contextual fear conditioning. In fact, the 0.3 mg/kg dose of MK-801 enhanced cued fear conditioning. Finally, rats were tested for MK-801-induced alterations in sensitivity to pain using the formalin test for nociception. MK-801 did not reduce sensitivity to pain. These results suggest that NMDA receptors are involved in acquisition of contextual fear conditioning but not in memory consolidation of the learned response.

Animals↗
PubMed1994

DBA/2 and C57BL/6 mice differ in contextual fear but not auditory fear conditioning.

It has been proposed that DBA/2 and C57BL/6 mice perform differently on some learning and memory tasks because of functional differences in the hippocampal formation. To evaluate this hypothesis, DBA/2 and C57BL/6 mice were tested on 2 forms of conditioned fear: contextual fear conditioning, which depends on the integrity of the hippocampal formation, and auditory cue conditioning, which does not. Both mouse strains displayed equivalent conditioning when the auditory cue was paired with shock, but DBA/2 mice showed significantly less conditioning to the context in which shock was experienced. These results are consistent with the hypothesis that the pattern of spared and impaired performance, which DBA/2 mice display on a variety of learning and memory tasks, is related to impaired hippocampal formation function.

Animals↗
PubMed2003

A twin study of the genetics of fear conditioning.

BACKGROUND: Fear conditioning is a traditional model for the acquisition of fears and phobias. Studies of the genetic architecture of fear conditioning may inform gene-finding strategies for anxiety disorders. The objective of this study was to determine the genetic and environmental sources of individual differences in fear conditioning by means of a twin sample. METHODS: Classic fear conditioning data were experimentally obtained from 173 same-sex twin pairs (90 monozygotic and 83 dizygotic). Sequences of evolutionary fear-relevant (snakes and spiders) and fear-irrelevant (circles and triangles) pictorial stimuli served as conditioned stimuli paired with a mild electric shock serving as the unconditioned stimulus. The outcome measure was the electrodermal skin conductance response. We applied structural equation modeling methods to the 3 conditioning phases of habituation, acquisition, and extinction to determine the extent to which genetic and environmental factors underlie individual variation in associative and nonassociative learning. RESULTS: All components of the fear conditioning process in humans demonstrated moderate heritability, in the range of 35% to 45%. Best-fitting multivariate models suggest that 2 sets of genes may underlie the trait of fear conditioning: one that most strongly affects nonassociative processes of habituation that also is shared with acquisition and extinction, and a second that appears related to associative fear conditioning processes. In addition, these data provide tentative evidence of differences in heritability based on the fear relevance of the stimuli. CONCLUSION: Genes represent a significant source of individual variation in the habituation, acquisition, and extinction of fears, and genetic effects specific to fear conditioning are involved.

Adult↗
PubMed2004

Contextual fear conditioning is associated with lateralized expression of the immediate early gene c-fos in the central and basolateral amygdalar nuclei.

Fos, the protein product of the immediate early gene c-fos, was used to map functional circuitry underlying contextual conditioned fear. Male rats were given footshocks in a distinctive context and later tested using freezing as the behavioral measure and compared with no-shock and no-retention-test control groups. An increased number of Fos-immunoreactive neurons was found in the lateral part of the central nucleus and in the anterior basolateral and lateral amygdalar nuclei in the brains of the conditioned-fear group compared with controls. Further, a greater number of Fos-immunoreactive neurons was observed in the right central and anterior basolateral nuclei compared with the number of labeled neurons in these structures on the left.

Amygdala↗
PubMed1992

Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.

The contribution of the amygdala and hippocampus to the acquisition of conditioned fear responses to a cue (a tone paired with footshock) and to context (background stimuli continuously present in the apparatus in which tone-shock pairings occurred) was examined in rats. In unoperated controls, responses to the cue conditioned faster and were more resistant to extinction than were responses to contextual stimuli. Lesions of the amygdala interfered with the conditioning of fear responses to both the cue and the context, whereas lesions of the hippocampus interfered with conditioning to the context but not to the cue. The amygdala is thus involved in the conditioning of fear responses to simple, modality-specific conditioned stimuli as well as to complex, polymodal stimuli, whereas the hippocampus is only involved in fear conditioning situations involving complex, polymodal events. These findings suggest an associative role for the amygdala and a sensory relay role for the hippocampus in fear conditioning.

Amygdala↗