"Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus": Correction to McNish et al (2000).

Reports an error in "Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus" by Kenneth A. McNish, Jonathan C. Gewirtz and Michael Davis (Behavioral Neuroscience, 2000[Feb], Vol 114[1], 64-76). The captions for Figure 4 (p. 70) and Figure 5 (p. 72) were printed incorrectly. The caption used for Figure 4 should appear under Figure 5, and the caption used for Figure 5 should appear under Figure 4. (The following abstract of the original article appeared in record 2000-13470-005.) The role of the dorsal hippocampus in contextual fear conditioning was investigated with a contextual blocking paradigm. In Experiment 1, rats were given pairings of a light conditioned stimulus (CS) and footshock after preexposure either to footshock or to the context alone. The group preexposed to footshock showed poorer fear conditioning to the light CS, as measured by the fear-potentiated startle reflex. In Experiment 2, a group preexposed to footshock in the same context showed poorer fear conditioning to the light CS than did a group preexposed to footshock in a different context, indicating contextual blocking of fear-potentiated startle. In Experiment 3, lesions of the dorsal hippocampus had no effect on contextual blocking, even though contextual freezing was disrupted. The sparing of contextual blocking indicated that contextual memory was intact following hippocampal lesions, despite the disruption of contextual freezing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of contextual fear conditioning in rats: Implications for consolidation, infantile amnesia, and hippocampal system function.

Presents developmental evidence that contextual fear conditioning is supported by a short-term memory system that supports conditioning immediately after a shock and by a long-term memory system that supports contextual conditioning 24 hrs after training. This is based on the finding that after 1 conditioning trial, rats 18–32 days old show the same amount of conditioned freezing when tested immediately after conditioning but 18-day-old rats show much less conditioned freezing than the older rats when the retention interval is 24 hrs. The data also suggest that the long-term memory representation of context that mediates conditioned fear is not available until several hours after the conditioning trial. Implications of these findings for memory consolidation processes, infantile amnesia, and hippocampal formation development are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Both pre- and posttraining excitotoxic lesions of the basolateral amygdala abolish the expression of olfactory and contextual fear conditioning

The present study examined whether the basolateral amygdaloid complex (BLA) participates in the expression of fear conditioned to both an olfactory conditioned stimulus (CS) and the training context. In Experiment 1, pretraining excitotoxic lesions of the BLA abolished immediate postshock freezing, conditioned freezing to an olfactory CS, and conditioned freezing to the training context. Control experiments indicated that lesioned and sham-lesioned subjects did not differ in locomotor activity or in acquisition of a successive-cue odor discrimination task, suggesting that deficits in freezing behavior exhibited by BLA subjects were not due to an impairment in primary aspects of olfaction or to a general enhancement of locomotor activity. In Experiment 2, excitotoxic lesions of the BLA produced either 1 day or 15 days after olfactory fear conditioning abolished both odor-elicited and contextual freezing. Collectively, these data support the notion that the BLA participates in an enduring manner in the expression of conditioned freezing behavior elicited by both olfactory and contextual stimuli.     

Effects of ethanol on encoding, consolidation, and expression of extinction following contextual fear conditioning.

Studies of contextual fear conditioning have found that ethanol administered prior to a conditioning session impairs the conditioned freezing response during a test session the next day. The present experiments examined the effects of ethanol on extinction, the loss of conditioned responding that occurs as the animal learns that a previously conditioned context no longer signals shock. Ethanol (1.5 g/kg) administered prior to single (Experiment 1) or multiple (Experiment 2) extinction sessions impaired extinction. Ethanol administered prior to a test session disrupted the expression of freezing after extinction (Experiments 3-5). There was some evidence that ethanol served as an internal stimulus signaling the operation of conditioning or extinction contingencies (Experiments 4-5). In Experiment 6, postsession injections of 1.5 g/kg ethanol had no effect on extinction with brief (3 min) or long (24 min) exposures to the context, but injections of 3 g/kg after long exposures impaired extinction. Together, these results indicate that ethanol affects extinction by acting on multiple learning and performance processes, including attention, memory encoding, and memory expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Expression of renewal is dependent on the extinction-test interval rather than the acquisition-extinction interval.

A recent finding suggested that when extinction occurs shortly after acquisition, renewal of an extinguished fear response (fear-potentiated startle) to a light conditioned stimulus (CS) is diminished (Myers, Ressler, & Davis, 2006). The present study attempted to extend this finding using a white-noise CS and freezing as the behavioral measure of fear. In Experiments 1A and 1B, we observed renewal whether extinction occurred 10 min or 24 hr after acquisition. In contrast, renewal was not observed if test occurred 10 min after extinction (Experiment 2). Experiment 3 demonstrated that expression of extinction at the 10-min extinction-test interval was attenuated by a pretest subcutaneous injection of the γ-aminobutyric acid (GABA) inverse agonist FG7142. These findings suggest that renewal is influenced more by the extinction-test interval than the acquisition-extinction interval. Further, the failure to see renewal 10 min after extinction suggests that there is a separate context memory that undergoes a different consolidation function than the CS-no US memory formed during extinction. Finally, the expression of extinction appears to be GABA dependent regardless of the extinction-test interval or the test context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus.

[Correction Notice: An erratum for this article was reported in Vol 114(2) of Behavioral Neuroscience (see record 2007-17251-001). The captions for Figure 4 (p. 70) and Figure 5 (p. 72) were printed incorrectly. The caption used for Figure 4 should appear under Figure 5, and the caption used for Figure 5 should appear under Figure 4.] The role of the dorsal hippocampus in contextual fear conditioning was investigated with a contextual blocking paradigm. In Experiment 1, rats were given pairings of a light conditioned stimulus (CS) and footshock after preexposure either to footshock or to the context alone. The group preexposed to footshock showed poorer fear conditioning to the light CS, as measured by the fear-potentiated startle reflex. In Experiment 2, a group preexposed to footshock in the same context showed poorer fear conditioning to the light CS than did a group preexposed to footshock in a different context, indicating contextual blocking of fear-potentiated startle. In Experiment 3, lesions of the dorsal hippocampus had no effect on contextual blocking, even though contextual freezing was disrupted. The sparing of contextual blocking indicated that contextual memory was intact following hippocampal lesions, despite the disruption of contextual freezing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence of contextual fear after lesions of the hippocampus: a disruption of freezing but not fear-potentiated startle

The roles of the dorsal hippocampus and the central nucleus of the amygdala in the expression of contextual fear were assessed using two measures of conditioned fear: freezing and fear-potentiated startle. A discriminable context conditioning paradigm was developed that demonstrated both conditioned freezing and fear-potentiated startle in a context paired previously with foot shock, relative to a context in which foot shock had never been presented. Post-training lesions of the central nucleus of the amygdala completely blocked both contextual freezing and fear-potentiated startle. Post-training lesions of the dorsal hippocampus attenuated contextual freezing, consistent with previous reports in the literature; however, these same lesions had no effect on fear-potentiated startle, suggesting preserved contextual fear. These results suggest that lesions of the hippocampus disrupt the freezing response but not contextual fear itself.     

An immediate-shock freezing deficit with discrete cues: A possible role for unconditioned stimulus processing mechanisms.

Five experiments with C57BL/6 mice (Mus musculus) investigated whether failures in shock processing might contribute to deficits in freezing that occur after an animal receives a shock immediately on exposure to a conditioning context. Experiment 1 found that more contextual freezing resulted from delayed shocks than from immediate shocks across 4 shock intensities. Experiment 2 extended the immediate-shock freezing deficit to discrete stimuli. Experiment 3 found that preexposure to the to-be-conditioned cue did not facilitate immediate cued conditioning. Experiment 4 found that context preexposure enhanced context-evoked fear after an immediate shock. Experiment 5 found that context preexposure also enhanced immediate cued conditioning. These findings are problematic for current theories of the immediate-shock freezing deficit that focus exclusively on processing of the conditioned stimulus, and they suggest that failures in shock processing may contribute to the deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immediate post-reminder injection of gamma-amino butyric acid (GABA) agonist midazolam attenuates reactivation of forgotten fear in the infant rat.

J. H. Kim, G. McNally, and R. Richardson (2006) reported that pretest injection of FG7142, a GABA inverse agonist, alleviated infantile amnesia in rats. From this, it was concluded that GABAergic neurotransmission is involved in the forgetting seen in the developing rat. The present study extends that finding by examining the role of GABA in the reactivation of a forgotten memory in the infant rat. Sixteen-day-old rats were conditioned to fear a white noise. When tested 3 days later, rats that had not received a reminder treatment exhibited substantial forgetting. Reactivation of memory (as assessed by high levels of freezing) was observed in rats that were given a reminder shock and injected with saline the day before test. However, rats given a reminder shock and injected with midazolam immediately afterward failed to exhibit the reactivation effect. A subsequent experiment replicated this finding and further showed that midazolam did not reduce the memory reactivation effect when injected 2 hr after the reminder episode. From this, it appears that alterations in GABAergic neurotransmission may be an underlying process mediating memory reactivation in the infant rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Odor-guided fear conditioning in rats: 1. Acquisition, retention, and latent inhibition.

Three experiments examined the acquisition, retention, and latent inhibition of odor-guided fear conditioning in rats. The results of Experiment 1 indicate that forward conditioned stimulus (CS)–unconditioned stimulus (US) pairings resulted in robust freezing responses to subsequent presentation of the CS alone. In Experiment 2, rats in one group (PRE) received unreinforced preexposures to the odorant CS, and those in a second group (NON) were not preexposed to the odorant. All rats then received forward CS–US pairings. PRE rats exhibited a marked attenuation of freezing to subsequent exposure to the CS relative to NON rats. All rats were then retested at one of the following posttraining delays: 17, 24, or 31 days. Freezing behavior of the NON rats declined significantly across these delays, whereas rats in the PRE group froze no more at any delay than they had 24 hr after training. Experiment 3 examined the contextual specificity of latent inhibition. Only those rats that were preexposed and were trained in the same context exhibited latent inhibition. These results indicate that odor-guided fear conditioning is a robust and useful paradigm suitable for future studies of the neural bases of associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Normal conditioning inhibition and extinction of freezing and fear-potentiated startle following electrolytic lesions of medial prefrontal cortex in rats.

The authors investigated the role of medial prefrontal cortex (mPFC) in the inhibition of conditioned fear in rats using both Pavlovian extinction and conditioned inhibition paradigms. In Experiment 1, lesions of ventral mPFC did not interfere with conditioned inhibition of the fear-potentiated startle response. In Experiment 2, lesions made after acquisition of fear conditioning did not retard extinction of fear to a visual conditioned stimulus (CS) and did not impair "reinstatement" of fear after unsignaled presentations of the unconditioned stimulus. In Experiment 3, lesions made before fear conditioning did not retard extinction of fear-potentiated startle or freezing to an auditory CS. In both Experiments 2 and 3, extinction of fear to contextual cues was also unaffected by the lesions. These results indicate that ventral mPFC is not essential for the inhibition of fear under a variety of circumstances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Water deprivation enhances fear conditioning to contextual, but not discrete, conditional stimuli in rats.

Water-deprived and nondeprived rats were fear conditioned with a discrete tone CS and an aversive footshock unconditioned stimulus/stimuli (UCS). 24 and 48 hrs following conditioning, conditional fear to the tone CS and the context cues of the conditioning chamber, respectively, were assessed by measuring freezing behavior. Water deprivation had no effect on baseline responding to either tone or contextual stimuli. Following either 1 or 3 tone-shock pairings, however, water deprivation selectively enhanced conditional freezing to the contextual cues of the training chamber; conditional freezing to the tone was unaffected by water deprivation. These results are consistent with the view that water deprivation affects fear conditioning via an influence on the hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disruptive effects of posttraining perirhinal cortex lesions on conditioned fear: Contributions of contextual cues.

Lesions placed in the rostral perirhinal cortex (rPRh) after fear conditioning interfere with the expression of conditioned fear responses elicited by auditory and visual conditioned stimuli when these stimuli are presented in a context that differs from the conditioning context. The present study examined whether lesions of the rPRh have similar effects when animals are tested in the conditioning context. Two days after male rats received classical fear conditioning, involving the pairing of an auditory CS with footshock, bilateral electrolytic lesions were produced in the rPRh. Five days later conditioned freezing behavior was measured during a 60-s exposure to the CS in a novel context and then 1 hr later in the conditioning context. There were 3 major findings: rPRh-lesioned Ss froze significantly less than controls to the CS in the novel context, thus confirming previously reported findings. rPRh-lesioned Ss also froze less than controls to the CS in the conditioning context, but froze significantly more to the CS in the conditioning than in the novel context, suggesting that at least part of the deficit in the novel context is due to the absence of contextual cues. Ss with rPRh lesions froze significantly less than controls to the conditioning context itself.… (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delayed extinction attenuates conditioned fear renewal and spontaneous recovery in humans.

This study investigated whether the retention interval after an aversive learning experience influences the return of fear after extinction training. After fear conditioning, participants underwent extinction training either 5 min or 1 day later and in either the same room (same context) or a different room (context shift). The next day, conditioned fear was tested in the original room. When extinction took place immediately, fear renewal was robust and prolonged for context-shift participants, and spontaneous recovery was observed in the same-context participants. Delayed extinction, by contrast, yielded a brief form of fear renewal that reextinguished within the testing session for context-shift participants, and there was no spontaneous recovery in the same-context participants. The authors conclude that the passage of time allows for memory consolidation processes to promote the formation of distinct yet flexible emotional memory traces that confer an ability to recall extinction, even in an alternate context, and minimize the return of fear. Furthermore, immediate extinction can yield spontaneous recovery and prolong fear renewal. These findings have potential implications for ameliorating fear relapse in anxiety disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reinstatement of Conditioned Fear in Humans Is Context Dependent and Impaired in Amnesia.

A contextual reinstatement procedure was developed to assess the contributions of environmental cues and hippocampal function in the recovery of conditioned fear following extinction in humans. Experiment 1 showed context specificity in the recovery of extinguished skin conductance responses after presentations of an auditory unconditioned stimulus. Experiment 2 demonstrated that fear recovery did not generalize to an explicitly unpaired conditioned stimulus. Experiment 3 replicated the context dependency of fear recovery with a shock as an unconditioned stimulus. Two amnesic patients failed to recover fear responses following reinstatement in the same context, despite showing initial fear acquisition. These results extend the known functions of the human hippocampus and highlight the importance of environmental contexts in regulating the expression of latent fear associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cycloheximide impairs reconsolidation of a contextually reactivated memory in a conditioned taste aversion paradigm.

Rats were used to examine the impact of systemic protein synthesis inhibition (PSI) on the reconsolidation of a contextually reactivated memory of conditioned taste aversion (CTA). Rats were administered intraperitoneal injections of saline or lithium chloride (LiCl; .15 M) following exposure to a novel sucrose solution in a unique context. Seven days later, rats were injected subcutaneously with saline or cycloheximide (CXM; 1 mg/kg) and returned to their home cage or placed into the CTA training context in the absence of the target conditioned stimulus to reactivate the training memory. At testing, LiCl-trained rats that had been given CXM at reactivation had significantly greater difference scores (sucrose-water) in comparison with LiCl/CXM rats that had not been given a reactivation treatment and LiCl/saline memory-reactivated rats. These results suggest that context re-exposure effectively reactivates memory of CTA training that may be weakened through PSI. Extinction tests revealed rapid attenuation of taste aversions in all of the LiCl-injected groups. The involvement of taste-potentiated aversions and the role of the context in taste aversion conditioning are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of training intertrial interval on acquisition of trace and long-delay fear conditioning in rats.

Many factors govern conditioning effectiveness, including the intertrial interval (ITI) used during training. The present study systematically varied the training ITI during both trace and long-delay fear conditioning. Rats were trained using one of six different ITIs and subsequently tested for conditioning to the white noise conditioned stimulus (CS) and the training context. After trace conditioning, percent freezing to the CS was positively correlated with training ITI, whereas percent freezing to the context was negatively correlated with training ITI. In contrast, when rats were trained using a long-delay paradigm, freezing during the CS test session did not vary as a function of training ITI; rats exhibited robust freezing at all ITIs. The long-delay conditioned rats exhibited relatively low levels of freezing during the context test. Thus, trace is more sensitive than long-delay fear conditioning to variations in the training ITI. These data suggest that training ITI is an important variable to consider when evaluating age or treatment effects, where the optimal ITI may vary with advancing age or pharmacological treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of forward or simultaneous conditioned stimulus-unconditioned stimulus intervals on the defensive behavior system of the Norway rat (Rattus norvegicus).

To test several predictions derived from a behavior-systems approach, the authors assessed Pavlovian fear conditioning in rats after 30 trials of forward, simultaneous, or unpaired training. Direct evidence of conditioned fear was collected through observation of flight and freezing reactions during presentations of the conditioned stimulus (CS) alone. The authors also tested the CS's potential to reinforce an instrumental escape response in an escape-from-fear paradigm. On the one hand, rats that received forward training showed conditioned freezing, but no conditioned flight was observed. On the other hand, rats that received simultaneous training showed conditioned flight, but no conditioned freezing was observed. Rats that received either forward or simultaneous pairings showed instrumental learning of the escape-from-fear response. Implications for several theories of Pavlovian conditioning are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reinstatement of extinguished fear by β-adrenergic arousal elicited by a conditioned context.

Five experiments examined the reinstatement of fear (freezing) produced by recent reexposure to a dangerous context. Rats were trained to fear a conditioned stimulus (CS) and a distinctive context with shock. The CS was then extinguished. A 2-min interval between reexposure to the dangerous context and presentation of the extinguished CS in a different context reinstated freezing when the CS was tested the next day. Propranolol (a β-adrenergic antagonist) blocked reinstatement of extinguished fear without decreasing freezing to a nonextinguished CS. Administration of epinephrine (an adrenergic agonist) reinstated extinguished fear without reexposure to the dangerous context. The results suggest a role for β-adrenergic activity elicited by exposure to a conditioned context in the reinstatement of extinguished fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Systemic mifepristone blocks reconsolidation of cue-conditioned fear; Propranolol prevents this effect.

Reducing reconsolidation of reactivated traumatic memories may offer a novel pharmacological treatment for posttraumatic stress disorder (PTSD). Preclinical research is needed to identify candidate drugs. We evaluated the ability of postreactivation mifepristone (RU38486, a glucocorticoid antagonist), alone and in combination with propranolol (a beta-adrenergic blocker), both given systemically, to reduce cue-conditioned fear in rats. On Day 1, a 30-s tone conditioned stimulus (CS) was paired with an electric shock unconditioned stimulus (US). On Day 2, the CS was presented without the US (reactivation), and the freezing conditioned response (CR) was measured. This was immediately followed by subcutaneous injection of vehicle, mifepristone 30 mg/kg, propranolol 10 mg/kg, or both. On Day 3, the CR was again measured as a test of postreactivation long-term memory (PR-LTM). On Day 10, the CR was again measured to evaluate spontaneous recovery. On Day 11, the US was presented alone (reinstatement). On Day 12, the CR was again measured. A fifth group received mifepristone without the CS presentation (nonreactivation) on Day 2. A sixth group was tested four hours after the Day 2 mifepristone injection to measure postreactivation short-term memory. Postreactivation, but not nonreactivation, mifepristone produced a decrement in the CR that did not undergo spontaneous recovery and underwent only modest reinstatement. Mifepristone did not exert its effect when administered concurrently with propranolol. Postreactivation mifepristone did not impair short-term memory. Systemic mifepristone blocks the reconsolidation of cue-conditioned fear in rats. Concurrent administration of propranolol prevents this effect. Postreactivation mifepristone may be a promising treatment for PTSD, but not necessarily in combination with propranolol. (PsycINFO Database Record (c) 2011 APA, all rights reserved)