Dorsal hippocampus involvement in trace fear conditioning with long, but not short, trace intervals in mice.

Placing a "trace" interval between a warning signal and an aversive shock makes consolidation of the memory for trace conditioning hippocampus dependent. To determine the trace at which memory consolidation requires the hippocampus, mice were trained with 0-s, 1-s, 3-s, or 20-s trace intervals and tested for freezing to context and tone. Posttraining dorsal hippocampus (DH) lesions decreased context conditioning regardless of trace interval. However, DH lesions attenuated only the 20-s trace tone freezing. Like eyeblink conditioning, the DH is necessary for trace fear conditioning only at long trace intervals, but the time scale for the effective interval in fear conditioning is about 40 times longer. Manipulations that alter trace fear conditioning with short trace intervals probably do not reflect altered DH function. Given this difference in time scale along with the use of posttraining DH lesions, hippocampus dependency of trace conditioning is not related to a bridging function or response timing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Central and basolateral amygdala neurons crash the aversive conditioning party: Theoretical comment on Rorick-Kehn and Steinmetz (2005).

Rorick-Kehn and Steinmetz (2005) (see record 2005-13804-012) report that neurons in the central and basolateral nuclei of the amygdala exhibit learning-related spike firing to conditional stimuli associated with shock in 3 different aversive conditioning paradigms: eyeblink conditioning, fear conditioning, and signaled avoidance conditioning. Central nucleus neurons responded in all 3 tasks, whereas basolateral nucleus neurons were more activated by fear and avoidance conditioning. These results reveal that amygdala neurons are differentially engaged by aversive conditioning, but questions remain concerning the associative basis and functional role for these unit responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immediate shock deficit in fear conditioning: Effects of shock manipulations.

Pavlovian contextual fear conditioning occurs when an aversive unconditional stimulus (US), such as a footshock, is presented to a rat shortly after it is placed in an experimental context. Contextual fear conditioning does not occur when the shock is presented immediately upon placement of the rat in the novel chamber. In the present study, the authors report that increasing either the number of immediate shock sessions (Experiment 1) or the immediate shock duration (Experiment 2) did not reverse this deficit. However, immediate shock seems to sensitize subsequent context conditioning (Experiment 3). These findings suggest that the associative deficit produced by immediate shock is not related to the rat's ability to process the footshock US. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prefrontal control of trace versus delay eyeblink conditioning: Role of the unconditioned stimulus in rabbits (Oryctolagus cuniculus).

The conditioned eyeblink (EB) response was studied with trace conditioning procedures in rabbits (Oryctolagus cuniculus) with lesions to the medial prefrontal cortex (mPFC) or sham lesions. Three experiments were performed in which either periorbital shock or a corneal airpuff served as the unconditioned stimulus (US) in separate groups of sham or mPFC-lesioned rabbits. Acquisition of the EB conditioned response (CR) was faster and reached a higher asymptote with the eyeshock US than with the airpuff US. However, mPFC lesion-induced trace conditioning deficits were obtained only in the groups that received the airpuff US. All rabbits showed normal delay conditioning and extinction. These results suggest that mPFC mediates trace EB conditioning when emotional arousal is low. However, in circumstances when emotional arousal may be high (i.e., during exposure to aversive periorbital shock), other structures (such as amygdala) may be activated to permit learning even in the absence of input from mPFC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Additional evidence for intact appetitive trace conditioning in hippocampal-lesioned rats.

Hippocampal lesions impair aversive trace conditioning but do not interfere with appetitive Pavlovian trace conditioning of the licking response (LR). This experiment examined whether learning to discriminate the events occurring in the home cage and in the training chamber could account for the differential effects of hippocampal lesions on aversive and appetitive trace conditioning. Performance of rats with excitotoxic lesions of the hippocampus was compared to that of sham-operated rats in LR trace conditioning. The unconditional stimulus (US) “cola soft drink” was delivered only in the training chamber. Thus, as in aversive conditioning procedures, the hedonic properties of the US and the resulting behaviors and motivational states occurred only in that environment. The results failed to reveal learning differences between lesioned rats and controls. Our findings and those of other reports concur that trace conditioning with an appetitive US is independent of the hippocampal system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning-specific reflex modification of the rabbit's nictitating membrane response and heart rate: Behavioral rules, neural substrates, and potential applications to posttraumatic stress disorder.

Interest in classical conditioning is usually focused on anticipatory responses to a stimulus associated with a significant event, and it is assumed that responses to the event itself are reflexive, involuntary, and relatively invariant. However, there is compelling evidence that both the rabbit nictitating membrane response (NMR) and heart rate response (HR), well-known reflexive reactions to aversive events, can change quite dramatically as a function of learning when measured in the absence of the conditioned stimulus. In the case of NMR conditioning, a simple blink is transformed into a larger and more complex response. For HR conditioning, reflexive heart rate acceleration can actually change to heart rate deceleration. In both cases, the reflex comes to resemble the conditioned response and follows some of the same behavioral laws. This change in response to the aversive event itself or weaker forms of that event is called conditioning-specific reflex modification (CRM). CRM may force us to reevaluate the behavioral and neural consequences of classical conditioning and may have important consequences for the treatment of conditions such as posttraumatic stress disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fischer 344 Rats Display Age-Related Memory Deficits in Trace Fear Conditioning.

A functional hippocampus is required for trace fear conditioning, which involves learning the association of a tone and shock that are separated over time. Young and aged rats received 10 trace conditioning trials. Twenty-four hours later, rats were tested for fear to the tone in a novel chamber by measuring freezing. The results showed significantly lower levels of freezing in aged rats as compared with young rats, which provides evidence of age-related memory impairments. Pseudorandom conditioning groups showed low levels of freezing, indicative of no associative memory. Age-related memory deficits were not found with delay conditioning, which suggests no age-related sensory-motor deficits. These data suggest that aging hinders the ability of the hippocampus to process information separated over time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The dorsal hippocampus is essential for context discrimination but not for contextual conditioning

The authors describe how (a) the timing of hippocampal lesions and (b) the behavioral-representational demands of the task affect the requirement for the hippocampus in contextual fear conditioning. Post- but not pretraining lesions of the hippocampus greatly reduced contextual fear conditioning. In contrast, pretraining lesions of the hippocampus abolished context discrimination, a procedure in which mice are trained to discriminate between 2 similar chambers (shock context vs. no-shock context). Whereas either contextual- or cue-based strategies can be used to recognize an aversive context, discrimination between similar contexts is optimally acquired by contextual (hippocampal)-based strategies. In keeping with the lesion results, Nf1(+/-)/Nmdar1(+/-) mutant mice, which have spatial learning deficits, are impaired in context discrimination but not in contextual conditioning. Together, these data dissociate hippocampal and nonhippocampal contributions to contextual conditioning, and they provide direct evidence that the hippocampus plays an essential role in the processing of contextual stimuli.     

Effects of lesions to the hippocampus on contextual fear: Evidence for a disruption of freezing and avoidance behavior but not context conditioning.

The effects of ibotenic lesions of the hippocampus on conditioning to contextual cues during classical fear conditioning in rats were evaluated by (a) the amount of freezing elicited by contextual cues and (b) the relative avoidance of a shock compartment. In Experiment 1, lesions to the hippocampus had no effect on contextual freezing and marginally affected avoidance after repeated sessions. Experiment 2 showed that lesions to the hippocampus disrupted avoidance when tested after a single conditioning session, while leaving unaffected the acquisition of contextual freezing. Experiment 3 indicated that these lesions decreased the acquisition of contextual freezing when higher footshock intensity was used but had no effect on avoidance after repeated conditioning sessions. These results show that freezing and avoidance do not quantify context conditioning similarly. They further indicate that lesions to the hippocampus may disrupt the expression of these behaviors used as measures of context conditioning but not the acquisition of context conditioning per se. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral self-control of smoking through aversive conditioning and self-management.

Evaluated self-control variants of aversive conditioning and self-management procedures for the modification of cigarette smoking. 16–37 yr old smokers (90% undergraduates) were assigned to 10 treatment conditions arranged in a 2?×?5 (Self-Management?×?Aversive Conditioning) factorial design; another 20 smokers were included in a no-apply control group. Five varieties of aversive conditioning were used: aversive conditioning, placebo shock, therapist-delivered shock, S-delivered shock, and imagined aversive scene. Half of the smokers under each variety of aversive conditioning received additional training in a package of self-management techniques. Smokers were seen by individual therapists in 6 sessions over 3 wks. The treatment effects of aversive conditioning were negligible, and in some instances they were surpassed by the effects of controls for nonspecific treatment factors and placebo effects. The addition of self-management to aversive conditioning significantly reduced smoking beyond aversive conditioning effects over a 20-wk follow-up. However, no treatment combination led to reductions in smoking beyond controls for nonspecific factors, nor were reductions maintained over follow-up times. Implications for behavioral self-control strategies are discussed. (49 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Morphine influences on classical aversive conditioned heart rate in rats.

Investigated in 3 experiments the effects of morphine and the morphine antagonist naloxone on the development of a classical aversive heart rate (HR) conditioned response (CR) to a tone conditioned stimulus (CS) paired with an electric shock unconditioned stimulus (US). In Exp I, groups of rats received either 0.25, 5 or 10 mg/kg, sc, of morphine. Three other groups were given 0.1, 5, or 10 mg/kg of naloxone. All morphine groups showed attenuation HR responses to the CS on preconditioning CS-alone trials. During conditioning, the 10-mg/kg morphine group showed a markedly decremented bradycardia CR and tachycardia unconditioned response (UR), whereas the 5-mg/kg morphine group showed a normal CR in combination with a decremented UR. In the Exp II, 1 mg/kg naloxone given after conditioning failed to reverse the CR and UR losses produced by 10 mg/kg of morphine given prior to conditioning. 10 mg/kg of morphine produced only a minor reduction in a HR CR established in a drug-free state, but the tachycardia UR was severely reduced. Exp III showed that 1 mg/kg of naloxone was effective in reversing analgesia induced by 10 mg/kg of morphine. 10 mg/kg dose of morphine interfered with the learning of a HR CR, perhaps principally by reducing the aversive or emotional consequences of the shock US. Direct cardiovascular effects of morphine seemed to interfere with the performance of the tachycardia UR, but not with the performance of the bradycardia CR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Timing of extinction relative to acquisition: A parametric analysis of fear extinction in humans.

Fear extinction is a reduction in conditioned fear following repeated exposure to the feared cue in the absence of any aversive event. Extinguished fear often reappears after extinction through spontaneous recovery. Animal studies suggest that spontaneous recovery can be abolished if extinction occurs within minutes of acquisition. However, a limited number of human extinction studies have shown that short interval extinction does not prevent the return of fear. For this reason, we performed an in-depth parametric analysis of human fear extinction using fear-potentiated startle. Using separate single-cue and differential conditioning paradigms, participants were fear conditioned and then underwent extinction either 10 min (Immediate) or 72 hr (Delayed) later. Testing for spontaneous recovery occurred 96 hr after acquisition. In the single cue paradigm, the Immediate and Delayed groups exhibited differences in context, but not fear, conditioning. With differential conditioning, there were no differences in context conditioning and the Immediate group displayed less spontaneous recovery. Thus, the results remain inconclusive regarding spontaneous recovery and the timing of extinction and are discussed in terms of performing translational studies of fear in humans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of meprobamate and prochlorperasine on positive and negative conditioning.

The comparative effect of 2 tranquilizing drugs (miltown and thorazine) upon conditioning in normal adults was investigated. Conditioning involved GSR to a noxious (shock) and positive (sexually stimulating picture) stimulus. Both tranquilizers were observed to be ineffective in affecting classical conditioning procedures when the noxious UCS was used. Only miltown effected conditioning in the predicted direction when the positive UCS was used. The results are related to the differential effect of each tranquilizer upon the nervous system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facial expressions of emotion as conditioned stimuli for human autonomic responses.

Used 26 undergraduates to test the hypothesis that congruity of a facial affective expression with an aversive outcome as compared to incongruity of an expression and outcome would result in superior differential conditioning of an autonomic response (skin conductance) to the facial expression. The study employed a differential conditioning paradigm with slides of fear faces and happy faces and CS+ and CS– or CS– and CS+, respectively. Findings are consistent with predictions. Both magnitude and rate of acquisition of the differential CR were greater when a fear expression was reinforced by shock than when a happy expression was reinforced by shock. (11 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In dubio pro defensio: Initial activation of conditioned fear is not cue specific.

This study explored the time course of conditioned fear response expression. Two neutral male facial expressions served as conditioned stimuli (CS) in a differential trace conditioning that involved either an aversive (n=14) or a nonaversive (n=12) unconditioned stimulus (UCS) in a between-subjects design. Skin conductance response (SCR) to the CSs and startle response magnitudes to acoustic probes presented at early (250 ms) or late (1,750 ms) probe times after CS onset were measured. As expected, conditioned SCR discrimination was observed in both aversive and nonaversive learning, whereas the conditioned potentiation of the startle response was only observed for the aversive UCS condition. Interestingly, conditioned startle discrimination was specific for the later probe time. In contrast, conditioned fear potentiation of the startle response at the early probe time was equally pronounced for CS+ and CS-. These findings suggest that fear-eliciting neural structures are rapidly activated in fear learning, whereas the expression of inhibitory conditioning requires more time, presumably reflecting the involvement of cortical top-down control processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disruption of Pavlovian contextual conditioning by excitotoxic lesions of the nucleus accumbens core.

Nucleus accumbens (NAcc) core lesions were performed either before or after Pavlovian aversive conditioning. NAcc core lesions had no effect on discrete-cue or contextual conditioned freezing during acquisition. During retention testing, neither pre- nor posttraining lesions had any effect on conditioned freezing to the discrete cue. However, pretraining lesions resulted in a profound impairment of contextual conditioned freezing in a retention test, and posttraining lesions resulted in a smaller impairment. NAcc core lesions had no effect on sensory or motor processes, as measured by shock reactivity and spontaneous locomotor activity. These results suggest that during acquisition, processes independent of the NAcc core mediate contextual conditioned freezing, but that the NAcc is implicated in the retention of this aversive memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Isolation and characterization of the human prosaposin promoter

Male C57BL/6N mice were chosen to determine Fos production during acquisition of context-dependent fear and after re-exposure to the conditioning context. Fear-conditioning was induced by a single exposure of mice to a context followed by an electric shock. Control groups consisted of mice exposed to context only (Context group) or to an immediate electric shock. When contextual retention was measured 24 h after conditioning (retention test 1), significant contextual generalization was observed. However, when animals were exposed to a different context from days 2-5 after conditioning and then tested for retention on day 6 (retention test 2), generalization was markedly reduced. After the training, the fear-conditioned mice produced higher Fos levels than mice exposed to an immediate shock in the hippocampus, medial amygdaloid nucleus and parietal somatosensory cortex. Both shock groups produced significantly more Fos than the Context group in the central nucleus of the amygdala. After retention test 1, fear-conditioned mice generated more Fos in the hippocampus and central amygdaloid nucleus than the two control groups. However, all groups exhibited similarly low Fos production after retention test 2. The results demonstrated that simultaneous Fos production in the hippocampus, central and medial nuclei of amygdala and somatosensory parietal cortex closely paralleled the ability of mice to acquire conditioned fear. In contrast, Fos production after the retention tests did not correlate with the expression of conditioned fear.     

Affective learning increases sensitivity to graded emotional faces.

How does the affective significance of emotional faces affect perceptual decisions? We manipulated affective significance by pairing 100% fearful faces with aversive electrical stimulation and hypothesized that increasing the significance of a stimulus via its prior history would lead to enhanced processing. After fear conditioning, participants viewed graded emotional faces that ranged from neutral to fearful. Faces were shown either in a color that was previously paired with shock or a color not paired with shock during conditioning. Increases in the frequency of "fearful" responses for faces shown in the shock-paired color were most robust for faces at intermediate intensity levels (40-60% fearful). Psychometric fits to the data revealed significant increased sensitivity for shock-paired relative to unpaired faces. Thus, despite identical physical features for shock-paired and unpaired stimuli (aside from the color, which was counterbalanced), more frequent (and faster) "fearful" responses were made when participants viewed affectively significant stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain indices of nonconscious associative learning

Using a classical conditioning technique, this study investigated whether nonconscious associative learning could be indexed by event-related brain activity (ERP). There were three phases. In a preconditioning baseline phase, pleasant and unpleasant facial schematics were presented in awareness (suprathreshold). A conditioning phase followed, in which stimuli were presented outside awareness (subthreshold, via energy masking), with an unpleasant face (CS+) linked to an aversive shock and a pleasant face (CS-) not linked to a shock. The third, postconditioning phase, involved stimulus presentations in awareness (suprathreshold). Evidence for acquisition of a conditional response was sought by comparing suprathreshold pre- and postconditioning phases, as well as in the subthreshold conditioning phase itself. For the pre-postconditioning phase analyses, significant ERP component differences differentiating CS+ and CS- were observed for N1, P2, and especially P3. For the conditioning phase, significant differences were observed in the 100-400 ms. post-stimulus region reflecting a CS+ processing negativity. Brain activity does indeed index the acquisition of a conditional response to subthreshold stimuli. Associative learning can occur outside awareness.     

Adenosine A? receptor activation selectively impairs the acquisition of contextual fear conditioning in rats.

Three experiments were conducted to examine the importance of adenosine A? receptors for the acquisition and expression of hippocampal-dependent and hippocampal-independent forms of conditioned fear. In Experiment 1, the selective adenosine A? receptor agonist, N?-cyclopentyladenosine (CPA), or saline was administered intraperitoneally to male rats 30 min prior to Pavlovian fear conditioning, which consisted of 7 tone–shock pairings. Adenosine A? receptor activation dose-dependently and selectively disrupted the acquisition of contextual fear conditioning while sparing tone–shock associations. Experiments 2 and 3 demonstrated that CPA's selective disruption of contextual learning could not be attributed to context being weaker than tone conditioning or to state-dependent learning. Adenosine A? receptor activation also impaired the expression of both context- and tone-elicited fear. These results suggest that endogenous adenosine modulates the acquisition and expression of emotional (fear) memories by acting on A? receptors in brain regions underlying fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)