Centrally administered corticotropin-releasing hormone and peripheral injections of strychnine hydrochloride potentiate the acoustic startle response in preweanling rats.

Attempts to condition fear potentiation of startle (FPS) in rats younger than 23 days of age have not been successful, regardless of the type of aversively conditioned stimulus used (P. S. Hunt, R. Richardson, & B. A. Campbell, 1994; R. Richardson, G. Paxinos, & J. Lee, 2000; R. Richardson & A. Vishney, 2000). In the present study, the authors report that peripheral injections of strychnine hydrochloride, a glycine receptor antagonist, and intracerebroventricular infusions of corticotropin releasing hormone (CRH) both potentiated the acoustic startle response (ASR) in 16–18-day-old rats. Because strychnine and CRH have distinct sites of activation in the primary startle pathway, it can be concluded that this pathway is functional and modifiable in rats younger than 23 days of age. This finding suggests that the failure to observe conditioned FPS in preweanling rats is due to an immaturity of the secondary fear circuit responsible for enhancing the ASR during a fear state. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The ontogeny of conditioned odor potentiation of startle.

During development, conditioned responses usually occur first to olfactory, then to auditory, and finally to visual cues. The authors of the present study report that fear potentiation of startle to an olfactory conditioned stimulus emerges relatively late in development (i.e., at 23 days of age; Experiments 1 and 2). The failure to observe conditioned odor potentiation of startle (OPS) in younger rats was not due to a failure to either acquire or remember the odor-shock association (Experiment 3). Surprisingly, the authors also found that rats trained at 16 but tested at 23 days of age failed to exhibit the OPS effect even though they did exhibit pronounced odor avoidance (Experiment 4). The results are discussed in terms of (a) sensory-specific sequential emergence of learned fear, (b) the neural circuit involved in fear potentiation of startle, and (c) the concept that conditioned responding is appropriate to the animal's age at the time of training rather than its age at testing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The ontogeny of fear-potentiated startle: Effects of earlier-acquired fear memories.

Research has shown that learned fear emerges in a response-specific sequence. For example, freezing is observed at a younger age than is potentiated startle (P. Hunt & B. A. Campbell, 1997). The present study shows that the age at which a specific learned fear response emerges is influenced by the animal's early experiences. Specifically, fear potentiation of startle emerges earlier in development if the rat is given prior fear conditioning to a different stimulus. Some constraints of this "facilitation" effect are determined in follow-up experiments. This facilitation effect may provide a novel way of testing the development of the neural circuits underlying learned fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pretraining Inactivation of the Caudal Pontine Reticular Nucleus Impairs the Acquisition of Conditioned Fear-Potentiated Startle to an Odor, but Not a Light.

Recent data from developing rats suggest that structures downstream from the amygdala are involved in the acquisition of conditioned fear-potentiated startle (FPS). The authors tested this idea in adult rats by temporarily inactivating the structure critical for FPS, the caudal pontine reticular nucleus (PnC), during fear conditioning. When the conditioned stimulus (CS) was an odor, rats displayed freezing, but not FPS, at test. This effect was not due to a decrease in footshock sensitivity. Further, no savings were evident on retraining. When the CS was a light, inactivation of the PnC had no effect on the acquisition of FPS. Thus, the PnC may be crucial for the acquisition of conditioned FPS to an odor, but not a light. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High Illumination Levels Potentiate the Acoustic Startle Response in Preweanling Rats.

Fear potentiation of the acoustic startle response (FPS) by aversive conditioned stimuli does not emerge in rats until Postnatal Day (P)23 (see P. S. Hunt & B. A. Campbell, 1997). However, the present study found that when presented with an unconditioned fear-eliciting stimulus, rats younger than P23 display FPS. Specifically, high illumination levels were found to enhance startle amplitudes in rats aged 18 and 25 days, but not 14 days. Furthermore, the light-enhanced startle observed in P18 rats was prevented by a systemic injection of the noradrenergic beta-receptor antagonist propranolol. These data suggest that conditioned and unconditioned FPS have different ontogenetic trajectories, and thereby provide support for the idea that learned and unlearned fear are subserved by dissociable neural systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning with masked stimuli affects the timecourse of skin conductance responses.

In Pavlovian fear conditioning, an aversive unconditional stimulus (UCS) is repeatedly paired with a neutral conditional stimulus (CS). As a consequence, the subject begins to show conditional responses (CRs) to the CS that indicate expectation and fear. There are currently two general models competing to explain the role of subjective awareness in fear conditioning. Proponents of the single-process model assert that a single propositional learning process mediates CR expression and UCS expectancy. Proponents of a dual-process model assert that these behavioral responses are expressions of two independent learning processes. We used backward masking to block perception of our visual CSs and measured the effect of this training on subsequent unmasked performance. In two separate experiments we show a dissociation between CR expression and UCS expectancy following differential delay conditioning with masked CSs. In Experiment I, we show that masked training facilitates CR expression when the same CSs are presented during a subsequent unmasked reacquisition task. In Experiment II we show that masked training retards learning when the CS+ is presented as part of a compound CS during a subsequent unmasked blocking task. Our results suggest that multiple memory systems operate in a parallel, independent manner to encode emotional memories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The expression of fear-potentiated startle during development: Integration of learning and response systems.

Relative to freezing, fear-potentiated startle (FPS) is developmentally delayed. Rats trained on Postnatal Day (PD) 18 expressed conditioned stimulus learning on PD 19 in freezing but not in FPS, whereas rats trained on PD 24 and tested on PD 25 expressed both freezing and FPS (Experiment 1). According to a neural maturation hypothesis, this delay results from functional immaturity of pathways mediating FPS. When rats were trained on PD 18, neither delaying the FPS test, allowing FPS pathways to develop, nor administrating the "reminder" treatment, the expression of FPS was promoted (Experiments 1, 2, and 2A). PD 18 learning was expressed in FPS on PD 25 when nontarget conditioned stimulus-unconditioned stimulus training occurred prior to the test, and this effect was modality dependent (Experiments 3 and 4). The authors conclude that engaging mechanisms of associative encoding when FPS pathways are functional is a critical condition for integrating learning and FPS response systems in development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delayed development of fear-potentiated startle in rats.

Examined the developmental emergence of fear-potentiated startle in rats ranging in age from 16 to 75 days. In Exp 1, a pure tone served as the CS and an acoustic startle pulse served as the unconditioned stimulus (UCS) for fear conditioning. Fear-potentiated startle by the tone CS was observed in rats 23 days of age and older but not in rats 16 days of age. In Exp 2, a light served as the CS. Rats 30 days of age and older showed fear-potentiated startle, whereas 23-day-old rats did not. The final experiment demonstrated that another behavioral index of fear, stimulus-elicited freezing, was observed earlier in development than fear-potentiated startle, confirming the effectiveness of the training procedure for conditioning fear. Results suggest that fear-potentiated startle is a relatively late-emerging response system, parallelling the development of conditioned autonomic changes (e.g., heart rate) rather than that of freezing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory-Mediated Fear Conditioning in Mice: Simultaneous Measurements of Fear-Potentiated Startle and Freezing.

This study demonstrates that mice display olfactory-cued fear as measured with both freezing and fear-potentiated startle. Following a preconditioning test to measure any unconditioned responses to odor, mice received 5 pairings of a 10-s odor with a 0.25-s, 0.4-mA footshock. The next day, startle and freezing were measured in the presence and absence of the odor. Both fear measures increased after training with amyl acetate (Experiment 1) and acetophenone (Experiment 2). The enhancement of startle did not occur when the same number of odors and shocks were presented in an unpaired fashion (Experiment 3). Furthermore, mice were able to discriminate between an odor paired with shock and a nonreinforced odor (Experiment 4). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Central CRF receptor antagonist α-helical CRF9-41 blocks reinstatement of extinguished fear: The role of the bed nucleus of the stria terminalis.

The present experiments assessed the necessity of central CRF in reinstatement of extinguished fear. Using the fear-potentiated startle procedure, rats were given light-shock pairings (fear conditioning) followed by light-alone extinction training. Rats were then given unsignaled shocks to reinstate fear to the light conditioned stimulus (CS). Intracerebroventricular administration of the CRF antagonist α-Helical CRF9-41 prior to reinstatement training dose-dependently prevented reinstatement. Further, α-Helical CRF9-41 administration prior to reinstatement training or the test for reinstatement of fear to the extinguished CS prevented reinstatement at both treatment times, suggesting that CRF activity is critical for this type of return of fear to an extinguished CS. The abolition of reinstatement by drug administration was not due to state-dependent learning, as rats treated with the drug prior to both reinstatement training or testing also failed α-Helical CRF9-41 in the bed nucleus of the stria terminalis suggested that this area is a site at which central CRF is involved in this form of relapse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of FG7142 on overexpectation of Pavlovian fear conditioning.

Six experiments studied the role of GABAA receptor activation in expression of overexpectation of Pavlovian fear conditioning. After separate pairings of CSA and CSB with shock in Stage I, rats received pairings of the compound AB with shock in Stage II, producing overexpectation of fear. The expression of overexpectation was attenuated, in a dose-dependent manner, by the benzodiazepine partial inverse agonist FG7142. FG7142 had no effect on responding to a CS paired with a low magnitude US or a CS subjected to associative blocking. These results suggest that the negative prediction error generated during overexpectation training may impose a mask on fear rather than erasing the original fear learning. They support claims that overexpectation shares features with extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned behavioral responses to a context paired with the predator odor trimethylthiazoline.

Contextual fear conditioning is the learning of a fear response in a specific context in response to repeated application of aversive stimuli (e.g., foot shocks) or danger-related stimuli (predator odors) within that context. Cat odor, a danger-related stimulus common in laboratory studies of fear in the past, has often been replaced recently with trimethylthiazoline (TMT), a component of fox feces. No contextual fear conditioning in response to TMT has been reported so far, whereas cat odor has often been shown to induce such fear conditioning in rats. Using TMT in both a 1-compartment and a 2-compartment setup, the authors found conditioned fear behavior (expressed as avoidance behavior) in the 2-compartment setup but not--as reported by others--in the 1-compartment setup. Detailed analysis revealed 2 different coping strategies in the 2-compartment setup: Half of the rats showed pronounced avoidance behavior, whereas the other half showed intense risk assessment behavior. These results indicate that expression of conditioned fear behavior in response to a TMT-paired context is dependent on the experimental setup used, as well as the strategy of the individual rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Six experiments studied the role of conditioned stimulus (CS) familiarity in determining the effects of the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 on fear extinction. Systemic administration of MK-801 (0.1 mg/kg) impaired initial extinction but not reextinction learning. MK-801 impaired reextinction learning when the CS was relatively novel during reextinction training but not initial extinction learning when the CS was relatively familiar during initial extinction training. A context change failed to reinstate the sensitivity of initial fear extinction learning about a relatively familiar CS to MK-801. These experiments show that CS familiarity is an important determinant of effects of MK-801 on fear extinction learning: MK-801 impaired extinction learning about novel stimuli but spared extinction learning about familiar stimuli. (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.     

Temporally massed CS presentations generate more fear extinction than spaced presentations.

Rodent fear conditioning models both excitatory learning and the pathogenesis of human anxiety, whereas extinction of conditional fear is a paradigm of inhibitory learning and the explicit model for behavior therapy. Many studies support a general learning rule for acquisition: Temporally spaced training is more effective than massed training. The authors asked whether this rule applies to extinction of conditional fear in mice. The authors find that both short- and long-term fear extinction are greater with temporally massed presentations of the conditional stimulus (CS). The data also indicate that once CS presentations are sufficiently massed to initiate, or "induce," extinction learning, further CS presentations are more effective when spaced. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual control of inhibition with reinforcement: Adaptation and timing mechanisms.

Four experiments with rats studied the effects of switching the context after Pavlovian conditioning. In three conditioned suppression experiments, a large number of conditioning trials created "inhibition with reinforcement" (IWR), in which fear of the conditional stimulus (CS) reached a maximum and then declined despite continued CS-unconditional stimulus pairings. When IWR occurred, a context switch augmented fear of the CS; IWR and augmentation were highly correlated. Neither IWR nor augmentation resulted from inhibition of delay (IOD): In conditioned suppression, IWR and augmentation occurred without IOD (Experiment 3), and in appetitive conditioning (Experiment 4), IOD occurred without IWR or augmentation. IWR may occur in conditioned suppression because the animal adapts to fear of the CS in a context-specific manner. The authors discuss several implications. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Odor-guided fear conditioning in rats: 2. Lesions of the anterior perirhinal cortex disrupt fear conditioned to the explicit conditioned stimulus but not to the training context.

Previous studies examining the neural substrates of fear conditioning have indicated unequivocally that the acquisition and expression of conditioned fear depends critically on the integrity of the amygdala. The extent to which the rhinal cortical areas contribute to fear conditioned to either the explicit conditioned stimulus (CS) or to the training context is less clear, however. The effects of pretraining lesions of the anterior perirhinal (PRH) cortex on fear conditioned to an explicit odor CS and to the context in which CS–unconditioned stimulus pairing took place was examined in rats. Rats with PRH cortex lesions demonstrated a robust attenuation of fear conditioned to the explicit CS, but no attenuation of fear conditioned to the training context. These data suggest that the PRH cortex is an important component of the neural system supporting the association between olfactory cues and footshock and add to a growing body of evidence implicating the rhinal cortical regions in associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cerebellar inactivation impairs cross modal savings of eyeblink conditioning.

Eyeblink conditioning using a conditioned stimulus (CS) from one sensory modality (e.g., an auditory CS) is greatly enhanced when the subject is previously trained with a CS from a different sensory modality (e.g., a visual CS). The enhanced acquisition to the second modality CS results from cross modal savings. The current study was designed to examine the role of the cerebellum in establishing cross modal savings in eyeblink conditioning with rats. In the first experiment rats were given paired or unpaired presentations with a CS (tone or light) and an unconditioned stimulus. All rats were then given paired training with a different modality CS. Only rats given paired training showed cross modal savings to the second modality CS. Experiment 2 showed that cerebellar inactivation during initial acquisition to the first modality CS completely prevented savings when training was switched to the second modality CS. Experiment 3 showed that cerebellar inactivation during initial cross modal training also prevented savings to the second modality stimulus. These results indicate that the cerebellum plays an essential role in establishing cross modal savings of eyeblink conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Single Neurons in the Dentate Gyrus and CA1 of the Hippocampus Exhibit Inverse Patterns of Encoding During Trace Fear Conditioning.

Trace fear conditioning is a hippocampus-dependent learning task that requires the association of an auditory conditioned stimulus (CS) and a shock unconditioned stimulus (US) that are separated by a 20-s trace interval. Single-neuron activity was recorded simultaneously from the dentate gyrus (DG) and CA1 of rats during unpaired pseudoconditioning and subsequent trace fear conditioning. Single neurons in DG showed a progressive increase in learning-related activity to the CS and US across trace fear conditioning. Single neurons in CA1 showed an early increase in responding to the CS, which developed into a decrease in firing later in trace conditioning. Correlation analyses showed that DG and CA1 units exhibit inverse patterns of responding to the CS during trace fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Predator odor-induced conditioned fear involves the basolateral and medial amygdala.

The basolateral (BLA) and medial nucleus (MeA) of the amygdala participate in the modulation of unconditioned fear induced by predator odor. However, the specific role of these amygdalar nuclei in predator odor-induced fear memory is not known. Therefore, fiber-sparing lesions or temporary inactivation of the BLA or MeA were made either prior to or after exposure to cat odor, and conditioned contextual fear behavior was examined the next day. BLA and MeA lesions produced significant reductions in cat odor-induced unconditioned and conditioned fear-related behavior. In addition, temporary pharmacological neural inactivation methods occurring after exposure to cat odor revealed subtle behavioral alterations indicative of a role of the BLA in fear memory consolidation but not memory retrieval. In contrast, the MeA appears to play a specific role in retrieval but not consolidation. Results show that the BLA participates in the conditioned and unconditioned cat odor stimulus association that underlies fear memory, underscore a novel role of the MeA in predator odor contextual conditioning, and demonstrate different roles of the BLA and MeA in modulating consolidation and retrieval of predator odor fear memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)