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Results for “fear conditioning”

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PubMed1999

Acquisition of fear conditioning in rats requires the synthesis of mRNA in the amygdala.

In this study, the role of mRNA synthesis in the amygdala was studied during the acquisition of conditional fear. Rats with cannulas placed in the basolateral region of the amygdala were trained with a series of noise-shock pairings in a distinctive observation chamber. One half of the rats were pretreated with the mRNA synthesis inhibitor actinomycin-D (act-D). Responding to the training context and the auditory stimulus in a novel context measured by defensive freezing was assessed. Pretreatment with act-D significantly attenuated fear responses to both stimuli. Animals receiving act-D injections exhibited normal reactions to the conditioned stimulus-unconditioned stimulus pairings in the initial training session and displayed normal learning when retrained 7 days after injections. These results indicate that the transcription of new mRNA and subsequent protein synthesis in the amygdala may be essential for neural plasticity during this form of associative learning.

Amygdala↗
PubMed1997

Converging evidence for one-trial context fear conditioning with an immediate shock: importance of shock potency.

In a sample of 208 Holtzman-descended albino rats, we found evidence with 4 measures of conditioning (freezing, defecation, side crossing, and nose crossing) that a single 2-s, 1.0-mA immediate shock could condition fear to a context (Experiments 1, 2, and 4). When we reduced the shock intensity to 0.5 mA, we obtained a complete immediate-shock conditioning deficit according to all measures in Experiment 3 and to all but the defecation measure in Experiment 4. Results suggest two conclusions: (a) Differences in shock potency between laboratories may help explain discrepant findings about whether immediate shock supports contextual conditioning; (b) theories of contextual conditioning need a mechanism that permits that conditioning to result from immediate shock.

Animals↗
PubMed1990

Pharmacological and anatomical analysis of fear conditioning.

The potentiated startle paradigm measures conditioned fear by an increase in the amplitude of a simple reflex (the acoustic startle reflex) in the presence of a cue previously paired with shock. This paradigm offers a number of advantages as an alternative to most animal tests of fear or anxiety, since it involves no operant and is reflected by an enhancement rather than a suppression of ongoing behavior. Lesion and electrical stimulation studies on fear-potentiated startle and startle increased by electrical stimulation of the amygdala are being used to define the neural pathways necessary for a visual conditioned stimulus to alter the acoustic startle reflex. The current working hypothesis is that the conditioned stimulus activates the central nucleus of the amygdala through a pathway involving the lateral geniculate nucleus and insular cortex. The central nucleus of the amygdala may then project directly to the acoustic startle pathway, modulating the startle response. More work has to be done to define conclusively the relevant neural pathways involved in fear-potentiated startle. Nonetheless, by combining behavioral, anatomical, physiological, and pharmacological approaches, it will be possible to determine each step along the pathway that mediates the ability of a stimulus signaling fear to alter behavior. Once the exact structures are delineated, it should be possible to determine the neurotransmitters that are released during a state of fear and how this chemical information is relayed along these pathways to affect behavior. Eventually, this approach should help to determine where plastic changes take place along these pathways to mediate the conditioned effects that are being measured and the biochemical processes that are involved.

Amygdala↗
PubMed2003

The substance P (NK1) receptor antagonist L-760735 inhibits fear conditioning in gerbils.

The ability of the substance P (NK(1) receptor) antagonist (SPA) L-760735 to inhibit conditioned fear was assessed in gerbils using a four plate apparatus. Animals that had been treated with diazepam (3 mg/kg) or L-760735 (3 mg/kg) 30 min before a 3 min conditioning session in the apparatus exhibited a release of plate crossings during the retest session approximately 3 h later. Plate crossings were also increased when animals received diazepam or L-760735 30 min before the retest session. In contrast, fluoxetine and venlafaxine (30 mg/kg) did not exhibit anxiolytic-like effects. During the retest session, gerbils drummed their hind feet on the floor; this behaviour was not observed spontaneously in gerbils that were naïve to the apparatus. Foot drumming was abolished by pretreatment with L-760735 or diazepam (3 mg/kg) but was markedly increased following administration of fluoxetine or venlafaxine (30 mg/kg). Foot drumming elicited by aversive conditioning alone or in combination with fluoxetine was abolished by administration of L-760735 and by amygdala lesions involving the basolateral and lateral nuclei, indicating that this behaviour is an alarm signal or fear response mediated via release of substance P in brain circuits involving the amygdala. The observations provide further evidence for an anxiolytic-like profile of SPAs in preclinical assays and demonstrate a clear difference between the actions of SPAs and established antidepressant drugs.

Amygdala↗
PubMedDate not supplied

Electrolytic lesions of the dorsal hippocampus disrupt renewal of conditional fear after extinction.

There is a growing body of evidence that the hippocampus is critical for context-dependent memory retrieval. In the present study, we used Pavlovian fear conditioning in rats to examine the role of the dorsal hippocampus (DH) in the context-specific expression of fear memory after extinction (i.e., renewal). Pre-training electrolytic lesions of the DH blunted the expression of conditional freezing to an auditory conditional stimulus (CS), but did not affect the acquisition of extinction to that CS. In contrast, DH lesions impaired the context-specific expression of extinction, eliminating the renewal of fear normally observed to a CS presented outside of the extinction context. Post-extinction DH lesions also eliminated the context dependence of fear extinction. These results are consistent with those using pharmacological inactivation of the DH and suggest that the DH is required for using contextual stimuli to regulate the expression of fear to a Pavlovian CS after extinction.

Animals↗
PubMed1994

Ontogeny of context-specific latent inhibition of conditioned fear: implications for configural associations theory and hippocampal formation development.

Latent inhibition of fear conditioning to an auditory cue, is measured by behavioral freezing, was examined in 18- and 23-day-old rats. In Experiment 1, CS preexposure and conditioning occurred in the same context for some rats but in a different context for other rats, and 24 hr separated CS preexposure and conditioning. The 23-day-old rats showed a context-specific latent inhibition effect, but the 18-day-old rats showed no latent inhibition. In Experiment 2, CS preexposure and conditioning occurred in the same training session and both 18- and 23-day-old rats showed latent inhibition. These results were discussed in relation to Wagner's (1976) theory of information processing, hippocampal formation maturation, and function, and Sutherland and Rudy's (1989) configural association theory.

Acoustic Stimulation↗
PubMed2004

Electrical stimulation of medial prefrontal cortex reduces conditioned fear in a temporally specific manner.

The authors recently showed that extinction of auditory fear conditioning leads to potentiation of tone-evoked activity of neurons in the infralimbic (IL) subregion of the medial prefrontal cortex, suggesting that IL inhibits fear after extinction (M. R. Milad, & G. J. Quirk, 2002). In support of this finding, pairing conditioned tones with brief (300-ms) electrical stimulation of IL reduces conditioned freezing. The present study showed that IL stimulation inhibits freezing if given 0.1 s after tone onset (the latency of tone-evoked responses) but has no effect if given either 1 s before or 1 s after tone onset. This suggests that IL gates the response of downstream structures such as the amygdala to fear stimuli.

Animals↗
PubMed1997

AMPA receptor facilitation accelerates fear learning without altering the level of conditioned fear acquired.

Rats treated with the AMPA receptor-facilitating drug 1-(quinoxolin-6-ylcarbonyl)piperidine (BDP-12) during training acquired fear conditioning to a tone faster than vehicle-treated controls. The effect on acquisition was dependent on the dose given. BDP-12-treated rats and vehicle-treated controls reached the same level of conditioned fear and extinguished at the same rate. The dissociation of learning rate from these other normally covariant measures suggests that the drug had a specific and isolated effect on acquisition. Controls for drug effects on stimulus sensitivity, locomotor activity, generalized fearfulness, and other performance factors support this interpretation. The known action of BDP-12 on receptor dynamics suggests that its effect on acquisition may be attributed to specific modulation of an AMPA and NMDA receptor-dependent plasticity mechanism. The finding that the drug accelerates acquisition but does not affect the level of conditioned fear acquired parallels the effect of the drug on long-term potentiation (LTP) (increasing the rate but not the ceiling of potentiation) and suggests that common mechanisms may underlie fear conditioning and LTP.

Animals↗
PubMed2006

Concurrent excitors limit the extinction of conditioned fear in humans.

In a human fear conditioning experiment, with on-line expectancy ratings and electrodermal responding as indices of fear, two neutral stimuli (pictures of geometric shapes) were first established as reliable predictors of an electric shock. In the subsequent extinction phase, the two stimuli were repeatedly presented in compound, without the shock. The final test phase consisted of individual stimulus presentations again, which resulted in a strong return of the conditioned responses. This effect was not observed in non-conditioned control stimuli. Hence, behavioral effects of extinction seem highly specific to the stimulus constellation that has gone through the extinction procedure. We argue that pharmacological, behavioral and/or cognitive manipulations that could prevent configural processing of stimulus constellations have direct clinical potential.

Conditioning, Psychological↗
PubMed2005

Effects of unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm on synaptic plasticity in the hippocampal CA1 area in vivo.

Repeated vivid recalls or flashbacks of traumatic memories and memory deficits are the cardinal features of post-traumatic stress disorder (PTSD). The underlying mechanisms are not fully understood yet. Here, we examined the effects of very strong fear conditioning (20 pairings of a light with a 1.5-mA, 0.5-s foot shock) and subsequent reexposure to the conditioning context (chamber A), a similar context (chamber B), and/or to the fear conditioned stimulus (CS) (a light) on synaptic plasticity in the hippocampal CA1 area in anesthetized Sprague-Dawley rats. The conditioning procedure resulted in very strong conditioned fear, as reflected by high levels of persistent freezing, to both the contexts and to the CS, 24 h after fear conditioning. The induction of long-term potentiation (LTP) was blocked immediately after fear conditioning. It was still markedly impaired 24 h after fear conditioning; reexposure to the conditioning chamber A (CA) or to a similar chamber B (CB) did not affect the impairment. However, presentation of the CS in the CA exacerbated the impairment of LTP, whereas the CS presentation in a CB ameliorated the impairment so that LTP induction did not differ from that of control groups. The induction of long-term depression (LTD) was facilitated immediately, but not 24 h, after fear conditioning. Only reexposure to the CS in the CA, but not reexposure to either chamber A or B alone, or the CS in chamber B, 24 h after conditioning, reinstated the facilitation of LTD induction. These data demonstrate that unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm can have profound effects on hippocampal synaptic plasticity, which may aid to understand the mechanisms underlying impairments of hippocampus-dependent memory by stress or in PTSD.

Animals↗
PubMed2006

Enhancement of conditioned fear extinction by infusion of the GABA(A) agonist muscimol into the rat prefrontal cortex and amygdala.

In auditory fear conditioning, repeated presentation of the tone in the absence of the shock leads to extinction of the acquired fear response. Both the infra limbic prefrontal cortex (IL) and the basolateral amygdala (BLA) are involved in extinction. In this study, we examine the involvement of these two regions in extinction by manipulating the gamma-aminobutyric acid (GABA)ergic system, in the Sprague-Dawley rat. We microinfused a low dose of the GABA(A) agonist muscimol into the IL or BLA. Muscimol infused to IL before extinction training, but not after either a short (five-trials) or long (15-trials) extinction training, resulted in long-term facilitation of extinction. Infusion of muscimol to the BLA following a short (five-trial) extinction session facilitated extinction at least 48-h post-drug infusion. The differences in the temporal parameters of the effects of muscimol in the IL or BLA, suggest differential involvement of these structures in long-term extinction of fear memory. We propose a facilitating role for GABA(A) neurotransmission in the IL in triggering the onset of fear extinction and its maintenance, whereas in the BLA, GABA(A) neurotransmission facilitates extinction consolidation. The involvement of GABA(A) receptors in fear extinction in the prefrontal cortex and amygdala is of particular interest, because of the role of these areas in emotional processes, and the role of the GABA(A) receptors in anxiety states.

Acoustic Stimulation↗
PubMed2002

Effect of chronic treatment with the protein kinase C inhibitor staurosporine on the acquisition and expression of contextual fear conditioning.

The present study investigated the effects of acute and chronic administration of the protein kinase C inhibitor, staurosporine, on the acquisition and expression of conditioned freezing behavior, an index of anxiety induced by conditioned fear stress. Results revealed that acute staurosporine (0.01 and 0.1 mg/kg, i.p.) did not affect either acquisition or expression of conditioned freezing. Chronic staurosporine administration (0.01 or 0.1 mg/kg, i.p., for 14 days) significantly reduced the acquisition of conditioned freezing at a dose of 0.1 mg/kg, but failed to affect the expression of conditioned freezing at any dose. These results suggest the involvement of protein kinase C in synaptic and cellular plasticity underlying emotional learning and memory.

Animals↗
PubMed2000

Exposure to a theta-burst patterned magnetic field impairs memory acquisition and consolidation for contextual but not discrete conditioned fear in rats.

Preceding or immediately following fear-conditioning rats were exposed for 30 min to either a sham field, one of two symmetrical (sine-wave 7, 20 Hz) magnetic fields or to one of two complex magnetic fields whose waveforms were modeled after salient electrophysiological patterns within either the hippocampal formation (theta-burst) or the amygdaloid complex (burst-firing). The magnetic fields were presented in successive 2s intervals through each of the three spatial planes and then simultaneously within all three planes. Field strengths ranged between 0.5 and 1 microTesla. Only the group exposed after the conditioning to the theta-burst (hippocampal) magnetic fields displayed evidence of forgetting, as inferred by their marked attenuation of freezing behavior, during contextual extinction 24h later. This powerful treatment explained 75% of the variance in the extinction scores. Behavioral responses to the discrete conditioned stimulus were not affected. These findings are consistent with the involvement of the hippocampus in learned fear to contextual stimuli but not to discrete auditory stimuli and suggest that physiologically relevant stimuli may be delivered to the brain by weak, complex magnetic fields whose intensities are ubiquitous within modern environments.

Acoustic Stimulation↗
PubMed2003

The role of NMDA glutamate receptors, PKA, MAPK, and CAMKII in the hippocampus in extinction of conditioned fear.

Pavlovian conditioning involves the association of initially neutral conditioned stimuli (CS) with unconditioned stimuli (US) that elicit a response. In contextual fear conditioning in rodents, the CS is the context of a training apparatus and the US is a foot shock. Retrieval of memory of the training is tested by presenting the CS alone. But a retrieval test also initiates extinction of the conditioned response. That is, presentation of the CS alone results in new learning, i.e., the CS no longer predicts the US. Here we report that extinction is triggered by two hippocampal signaling pathways underlying retrieval (the cAMP-dependent protein kinase and the mitogen-activated protein kinase pathways) and two other mechanisms that become activated at the same time and are not necessary for retrieval (N-methyl-D-aspartate glutamatergic receptors and the calcium/calmodulin-dependent protein kinase II signaling pathway). Thus, the molecular mechanisms underlying acquisition and/or consolidation of the memory for extinction are similar to those described for the acquisition and/or consolidation of the original contextual fear.

Animals↗
PubMed2002

Conditioned memory modulation, freezing, and avoidance as measures of amygdala-mediated conditioned fear.

Three conditioned aversive responses were used to infer the existence of an unobservable central state of "conditioned fear," and the roles of certain amygdala subregions in producing these responses were investigated. Rats received tone-shock pairings in one compartment of a shuttle box and no tones or shocks in the other, distinctive, compartment. They were then trained to find food in one arm of a Y-maze. After the final training trial they were exposed to different sets of stimuli in the shuttle box with no shock. Twenty-four hours later rats that had received immediate posttraining exposure to the conditioned stimuli (in the shock-paired compartment) made significantly more correct responses on the Y-maze than rats that had been exposed to the neutral stimuli (in the no-shock compartment) or rats that had received delayed posttraining exposure to the conditioned stimuli. This constitutes a demonstration of posttraining memory modulation by conditioned aversive stimuli. Freezing increased during posttraining exposure to the conditioned stimuli compared to the neutral stimuli. When subsequently allowed to move freely between the two compartments, the rats in all groups also showed significant conditioned avoidance of the compartment containing the conditioned stimuli. In a second experiment the effects of lesions confined to specific parts of the amygdala on the three conditioned responses (memory modulation, freezing, avoidance) were tested. Lesions of the central nucleus impaired all three conditioned responses; lesions of the medial nucleus impaired conditioned modulation and avoidance. These lesions had no effect on freezing during the training trials. Lesions of the lateral and basolateral nuclei attenuated freezing during both training and testing. The findings suggest that the central and medial nuclei of the amygdala may be important parts of neural circuits mediating conditioned responses that constitute conditioned aversive states, but that conditioned freezing may be mediated independently.

Acoustic Stimulation↗
PubMed2001

The ventral hippocampus and fear conditioning in rats: different anterograde amnesias of fear after infusion of N-methyl-D-aspartate or its noncompetitive antagonist MK-801 into the ventral hippocampus.

Previous studies on hippocampal involvement in classical fear conditioning mainly focused on the dorsal hippocampus and conditioning to a context. However, in line with the strong interconnectivity of the ventral hippocampus with amygdala and nucleus accumbens, more recent studies indicated an even more global role for the ventral hippocampus in fear conditioning. The present study examined the formation of classical fear conditioning to explicit and contextual cues following stimulation or blockade of N-methyl-D-aspartate (NMDA) receptors in the ventral hippocampus. NMDA (0.5 microg/side) or the noncompetitive NMDA antagonist MK-801 (dizocilpine; 6.25 microg/side) were bilaterally infused into the ventral hippocampus of Wistar rats before fear conditioning to explicit and contextual cues. Conditioned fear was assessed using an automated measurement of freezing. NMDA stimulation of the ventral hippocampus blocked fear conditioning to both the tone and the context. MK-801 selectively blocked fear conditioning to the context. Our results support that the ventral hippocampus plays a role in the formation of classical fear conditioning. The specific anterograde amnesia for fear to a context after MK-801 infusion into the ventral hippocampus indicates that formation of classical fear conditioning to a context but not to a tone requires activation of NMDA receptor-mediated processes in the ventral hippocampus. Given that NMDA stimulation of the ventral hippocampus disrupts also processes not mediated by NMDA receptors, the complete anterograde amnesia following NMDA infusion into the ventral hippocampus might be due to the concurrent severe disruption of normal ventral hippocampal activity. However, strong stimulation of the ventral hippocampus might also disrupt fear conditioning by interfering with processes in the projection areas of the ventral hippocampus, such as the amygdala or the nucleus accumbens. In addition, we report that MK-801 (6.25 microg/side) infusion into the ventral hippocampus increased locomotor activity in the open field.

Amygdala↗
PubMed2001

The ventral hippocampus and fear conditioning in rats. Different anterograde amnesias of fear after tetrodotoxin inactivation and infusion of the GABA(A) agonist muscimol.

Studies on the involvement of the rat hippocampus in classical fear conditioning have focused mainly on the dorsal hippocampus and conditioning to a context. However, the ventral hippocampus has intimate connections with the amygdala and the nucleus accumbens, which are involved in classical fear conditioning to explicit and contextual cues. Consistently, a few recent lesion studies have indicated a role for the ventral hippocampus in classical fear conditioning to explicit and contextual cues. The present study examined whether neuronal activity within the ventral hippocampus is important for the formation of fear memory to explicit and contextual cues by classical fear conditioning. Tetrodotoxin (TTX; 10 ng/side), which completely blocks neuronal activity, or muscimol (1 microg/side), which increases GABA(A) receptor-mediated inhibition, were bilaterally infused into the ventral hippocampus of Wistar rats before the conditioning session of a classical fear-conditioning experiment. Conditioning to a tone and the context were assessed using freezing as a measure of conditioned fear. TTX blocked fear conditioning to both tone and context. Muscimol only blocked fear conditioning to the context. The data of the present study indicate that activity of neurons in the ventral hippocampus is necessary for the formation of fear memory to both explicit and contextual cues and that neurons in the ventral hippocampus that bear the GABA(A) receptor are important for the formation of fear conditioning to a context. In addition, both bilateral muscimol (0.5 microg/side and 1 microg/side) and TTX (5 ng/side and 10 ng/side) infusion into the ventral hippocampus dose-dependently decreased locomotor activity in an open-field experiment.

Acoustic Stimulation↗
PubMed1999

Pain pathways involved in fear conditioning measured with fear-potentiated startle: lesion studies.

It is well established that the basolateral amygdala is critically involved in the association between an unconditioned stimulus (US), such as a foot shock, and a conditioned stimulus (CS), such as a light, during classic fear conditioning. However, little is known about how the US (pain) inputs are relayed to the basolateral amygdala. The present studies were designed to define potential US pathways to the amygdala using lesion methods. Electrolytic lesions before or after training were placed in caudal granular/dysgranular insular cortex (IC) alone or in conjunction with the posterior intralaminar nuclei of the thalamus (PoT/PIL), and the effects on fear conditioning were examined. Pretraining lesions of both IC and PoT/PIL, but not lesions of IC alone, blocked the acquisition of fear-potentiated startle. However, post-training combined lesions of IC and PoT/PIL did not prevent expression of conditioned fear. Given that previous studies have shown that lesions of PoT/PIL alone had no effect on acquisition of conditioned fear, these results suggest that two parallel cortical (insula-amygdala) and subcortical (PoT/PIL-amygdala) pathways are involved in relaying shock information to the basolateral amygdala during fear conditioning.

Animals↗